生命由一連串生化反應來維持, 而生物分子組成負責特定生化反應的生物機器來維持生命。本文詳細闡述了三種參與DNA/mRNA/tRNA/rRNA結合（bind）、解旋(unwind)、折彎(kink)、滾動(roll)之奈米機器其作用的機械化學(mechanochemical)細節:(1)一個從古生菌 Sulfolobus acidocaldarius來的不具核酸選擇性，能以大角度折彎 DNA的蛋白, Sac7d, (2)一個不需消耗ATP即可解旋雙股DNA的人類TDP-43的RNA辨認蛋白(RNA Recognition Motifs; RRM1 and RRM2)/(chaperon),(3)prokaryotic ribosome :在核糖體轉譯框架位移(programmed ribosomal frameshifting, PRF)的過程中，一個受偽結(PRF- stimulating pseudoknot,PK)誘發而進行滾轉運動(rolling motion) 的原核核糖體。
在Sac7d的研究中,我們在分子層面上解釋了Sac7d如何找到單股DNA的小溝(minor groove)並與其結合,進而使單股DNA折彎。在分子動力模擬的結果中，當Sac7d結合在雙股DNA的小溝後, Sac7d與雙股DNA間的空隙中會出現三個水分子的結合位.而該空間對外的通道會被Sac7d中R42殘基所阻塞。這三個水分子驅動了DNA鹼基對的翻轉而導致雙股DNA的折彎。 這樣的翻轉使Sac7d 的V26及M29殘基有機會嵌入DNA鹼基堆疊（base stacks）中，進一步加劇了這個折彎現象, 最終的滾動角度(roll angle)達到69.1°。這個結果也與文獻上X-ray 結晶學解析出的3D結構(PDB: 1AZP)的61.3°符合，而三個驅動反應的水分子也同樣在該結構中被發現。計算模擬中水分子、V26與及M29殘基的總受力(65.9 pN)與先前使用光鉗將堆疊的B-DNA核糖鹼基從3.4 Å拉開到5.8 Å的實驗所量測到的65.0 pN也非常相近。這結果顯示三個被困在Sac7d與雙股DNA間的空隙中水分子架開了鄰近的鹼基堆疊，進而驅動了Sac7d折彎雙股DNA。
RRM1與RRM2是兩個RRMs motifs有相似的三級結構，兩者均能與RNA與單股DNA結合，但是兩者序列的相似度(sequence identity)僅有約30%。藉由分析RRMs-RNA/ssDNA分子動力模擬得到每個殘基、核酸的結合能並參考突變及EMSA實驗資料,發現RRM1對於RNA/ssDNA的結合能力皆高於RRM2，並且RRMs結合RNA的能力高過結合（相對應的）ssDNA的能力。在模擬結果顯示RRM1具有在不消耗ATP的情況下解旋並打開ds(TG)¬6的能力,而與RNA結合力較弱的RRM2卻不具有此功能。在多重序列分析後發現，RNA結合位上殘基在演化上具有最高保守度其次參與單股DNA結合的殘基,最後才是參與雙股DNA結合的殘基。這個分析暗示了負責單股/雙股DNA結合/解旋的蛋白質很可能是由RNA伴護因子(chaperoning)修改少數的殘基序列得來。這個推測與生物演化是由“只有RNA與蛋白質”系統到“RNA，蛋白質及DNA”系統的假說不謀而合。
細菌、病毒經常能夠利用一個mRNA模板並配核醣體轉譯框架位移(PRF)來合成不同的蛋白質。PRF已知是由轉譯中mRNA所形成的特殊立體結構，偽結(PRF-stimulating pseudoknot, PK)誘導產生。為了探討在PRF現象發生時，RNA解旋酶的活性與核醣體的構型變化在其中的作用，我們利用跨尺度分子動力學模擬（resolution-exchanged MD simulations）及線性相應理論（linear response theories ，LRT)建構了一個分子模型，並整合文獻上的X-ray結構、單分子螢光共振實驗（single molecule FRET analysis）以及突變實驗數據來闡述PRF的過程。當核醣體嘗試解開偽結(pseudoknot)時,它的mRNA入口處會受到來自偽結的作用力來重組核醣體的固有動態，產生構型改變。我們發現這個構型變化主要是30S次單位的滾動(rolling)，擠壓了反應中的tRNAs至使tRNA從0-frame滑動至1-frame，最終導致PRF。
另外，我們還開發了兩項生物資訊工具分別用於1.設計具有療效的胜肽2.偵測抄襲剽竊。在設計療效胜肽方面，我們從protein data bank (PDB)的所有蛋白質結構中,萃取出一百七十萬條二級結構為螺旋的胜肽 (helical peptides, HPs)還有與這些HPs在結構中有交互作用或互相接觸的HPs。我們以特別設計的樣式(如Y3G2K可以表示所有符合Y***G**K格式的序列 , A1,2K2G表示所有符合A*/**K**G樣式的序列等, *表示任意氨基酸)索引這些胜肽的氨基酸序列,並把HPs的資訊 (PDB ID、chain ID, 胜肽的起始跟結束的序號) 與索引對應後存入資料庫。我們利用這個HPs資料庫, 分別以K3G2Y、A3K3G2Y、K3G2Y3A、A2,3K2,3G2,3Y2,3A為模板，撈出了69、3、2、3條具抗癌潛力的胜肽。這些胜肽可以干擾PP2A與Sgo1的結合面上所依賴的螺旋-螺旋交互作用 (helix-helix interaction)，主要是以與PP2A的競爭Sgo1上結合位為概念而設計。接著用粗粒化(coarse-grained)及全原子的分子動力模擬，MM-PBSA，再將撈出胜肽進一步做篩選及排序。未來我們將用isothermal titration calorimetry (ITC)、FRET、NMR、CD 光譜來分析篩選後的HPs與Sgo1的結合能力。另外，我們使用HPs資料庫尋找先前發現的具有在POPC雙層磷脂質膜上折疊並嵌入膜中能力的螺旋樣式 (W2W2W、 K2R0W2W、W1WW2W與W2WW1W)，並挑選正電及與其他部分接觸較少的HPs來進行實驗測試。由minimal inhibitory concentration (MIC)實驗結果顯示，這些選中的HPs具有抗菌能力。
SAVE是一個以生物序列為概念核心，所開發的反剽竊工具。它具有強大的隱私保護功能及新設計的索引及檢索方法。為了達到隱私保護我們引入了生物資訊常用的演算方法，如BLAST與動態規劃演算法(Dynamic Programming, DP)。在偵測兩文件是否有抄襲時，文件中的中、西方文字會以“字”為單位（忽略常用字，如”the”、”a”、”and”等），我們會用一種不可逆(undecodable)的編碼法將所有內文轉換成偽生物序列（pseudo-biological sequences，PBSs）。透過我們所開發的客戶端桌面應用程式（SAVE_App），對於欲使用SAVE隱私比對文件的使用者，我們讓用戶在非網路環境下就可以轉換機密文件以降低洩露文章內容的風險。若只是一般文件互相比對，用戶可以直接上傳文件到SAVE網路服務器，在SAVE會直接將文件的內文萃取後，轉換為PBSs。然後以經過參數最佳化後的BLAST執行比對工作，最佳化主要針對搜尋與query有連續12個字或以上相同的序列。這些在PBSs相同序列的區域，我們會在原文標記為潛在抄襲內容(若隱私模式，則由SAVE_App完成在原文上的標記)。不管隱私模式還是非隱私模式，SAVE還可以將文章與網際網路的內容進行比對。關於隱私模式，我們首先將所有常被抄襲的網站（如Wikipedia）的內容轉換為PBSs並建立有效索引算法及高速的比對算法來確認用戶文件內容的PBSs是否有跟資料庫現有的PBSs有重疊。比對完若有較長重疊，則視為潛在抄襲內容，SAVE_App亦會在客戶端將潛在抄襲內容標記於原文檔中。對於非隱私模式，我們會將文件內容切成可以被Google搜尋引擎API搜尋的小段落。搜尋結果經SAVE服務器運用動態規劃算法(dynamics programming)與原文比對後，若發現有網際網路上的內容有與小段落有連續12個或以上的字相同時，該內容的原文區域將會被標記為潛在抄襲內容。

Biological machines are biomolecules that are capable of facilitating specific biochemical processes that support life. We elucidated the mechanochemical details of molecular functions for three nanomachines that bind, unwind, kink and roll DNA/mRNA/tRNA/rRNA: [1] archaeal DNA kinking protein (DKP), Sac7d, from Sulfolobus acidocaldarius which sharply bends, i.e. kinks, double-stranded DNA (dsDNA) in a sequence general manner; [2] RNA Recognition Motifs (RRM1 and RRM2) of human TDP-43 (TAR (trans-activation response element) DNA-binding protein 43), which have stronger binding affinity for RNA than for single-stranded DNA (ssDNA), with RRM1 exhibiting ATP-independent dsDNA helicase activity; and [3] prokaryotic ribosome which, during programmed ribosomal frameshifting (PRF), exhibits a rolling motion triggered by a PRF-stimulating pseudoknot (PK).
In the Sac7d studies, we examined the molecular details of how dsDNA is approached, captured in its minor groove, and kinked by Sac7d. Three water molecules are trapped in a water pocket between Sac7d and dsDNA's minor groove in the final stage of the capturing when R42 closes the channel that links the water pocket to the bulk solvent. These catalytic water molecules actively initiate dsDNA kinking by exerting forces on the dsDNA leading to the flipping of the nucleotides' base stacks. The water-initiated dsDNA kinking is further enhanced when Sac7d's V26 and M29 intercalates between the bases resulting in a roll angle of up to 69.1° which agrees with X-ray crystallization results (61.3°; PDB: 1AZP) while the confined and stabilized catalytic water molecules found by MD simulations are co-localized with those observed in the protein crystal. The summed forces (65.9 pN) from the water molecules, V26, and M29 are comparable to that obtained from previous optical tweezers experiments (65.0 pN) in which a pair of stacked nucleotide bases were unstacked and stretched from 3.4 Å to 5.8 Å in the B-DNA. Our results indicate that strategically trapped catalytic water molecules play active roles in dsDNA kinking by Sac7d.
While studying the RRMs of TDP-43, we observed that RRM1 and RRM2 (which are structurally identical but with distinct sequences - ~30% sequence identity) have RNA and ssDNA binding affinities that differ by two orders of magnitude. Residue-level and nucleotide-level decomposition of the protein-RNA/ssDNA binding energies obtained from MD simulations together with mutagenesis data and EMSA data demonstrate that RRM1 binds RNA/ssDNA stronger than RRM2, while RRMs bind RNA stronger than they bind DNA. MD results suggest that RRM1 can unwind ds(TG)6 thereby exhibiting an ATP-independent dsDNA helicase activity, while RRM2, a weaker RNA binder, cannot. Furthermore, we observed a high resemblance in the ssDNA and RNA binding sites of the RRMs, but only a partial overlap with their dsDNA binding sites. Multiple sequence analysis shows that the RNA binding residues are the most evolutionarily conserved, followed by the ssDNA binding residues, while the dsDNA binding residues are the least evolutionarily conserved. These suggest the possibility of ss/dsDNA binding/unwinding activities easily evolving from a strong RNA chaperoning functionality with minimal residue modifications, which is consistent with the speculated evolution of life from a "RNA and protein only” system into a "RNA, protein, and DNA” system.
In our study of the RNA helicase activities and the conformational dynamics of the ribosome in the context of PRF, a mechanism widely used by bacteria and viruses for producing different proteins using one mRNA template, we used resolution-exchanged MD simulations and linear response theories (LRT) for constructing a molecular model that integrates and rationalizes existing structural, single-molecule, and mutagenesis data to elucidate the PRF. We observed that, while the ribosome unwinds PRF-stimulating PK, the ribosomal mRNA entrance experiences resistant forces from the PK unwinding. The resistant forces modify the conformational dynamics of the ribosome, causing the 30S ribosomal subunit to roll, which in turn compresses the tRNAs, leading to tRNA slippage from the 0-frame into the -1 frame, thereby causing PRF.
In addition, we developed bioinformatics tools [1] for designing therapeutic peptides and [2] for detecting plagiarism. For the therapeutic peptides project, we extracted 1.7 million helical peptides (HPs) and their interacting/contacting partners from the protein data bank (PDB). The sequences of the HPs were developed into a searchable database (HP-DB) by creating indexes that map peptide patterns (such as Y***G**K which is equivalent to Y3G2K, A*/**K**G="A1,2K2G", etc.) to their locations in PDB structures, defined by the PDB ID, the chain ID, and the index of the position where the pattern begins in the protein's chain. Using the developed HP-DB, coarse-grained, all-atom MD simulations, and MM-PBSA, we examined and ranked the potential anti-tumor peptides (69 from the K3G2Y pattern, 3 from A3K3G2Y, 2 from K3G2Y3A, and 3 from "A2,3K2,3G2,3Y2,3A") that could out-compete PP2A in its helix-mediated interaction with Sgo1. The top peptides are selected for further interaction analysis by wet lab experiments such as isothermal titration calorimetry (ITC) and FRET ITC and NMR. CD spectrum. In another application of the developed HP-DB, which is based on our earlier observation that an extended peptide with WLK repeats could fold into α-helix on top of POPC lipid bilayer and insert into the upper leaflet of lipid bilayer, we searched for peptides with W2W2W, K2R0W2W, W1WW2W, and W2WW1W patterns and selected positively charged motifs with relatively low coordination numbers for experimental tests. The minimal inhibitory concentration (MIC) of the newly designed peptide clearly suggested its anti-fungal activity.
Inspired by biological sequences, we developed SAVE - A Plagiarism Detection Tool with Enhanced Privacy Protection, which makes use of known bioinformatics algorithms (such as BLAST and Dynamic Programming) and a new data indexing and searching method we have developed. For pairwise comparison of documents for potential plagiarism, we encode the words in each of the documents (excluding the common words such as "a", "the", "and", etc.) into pseudo-biological sequences (PBSs) in a way that each western or eastern “word” is encoded into one of 8 English alphabets (or “pseudo-amino acids”, resulting in degenerated PBSs that could not be reverted to form the original documents. We developed a local SAVE Desktop Application (SAVE_App) for the users to convert documents into PBSs directly on their computers whenever the users intend to use SAVE in private mode, otherwise, users can directly submit their documents to SAVE's web server where the PBSs are automatically generated when using the non-private mode. The pairwise comparisons of the PBSs are carried out using carefully parameterized BLAST. A potential plagiarism is flagged whenever a pair of PBSs have 12 or more continuous overlaps. The start and end positions of the regions of the continuous overlaps are then used to highlight the potentially plagiarized part in the original documents using SAVE_App (locally on the user's computer) in private mode, or directly on the SAVE web server in the non-private mode. In addition to the pairwise plagiarism detection, any document can be checked for potential plagiarism against the contents on the WWW (internet search) in the private or in the non-private mode. For the private mode internet search, we created PBSs for WWW contents starting with the commonly plagiarized pages (such as Wikipedia pages and peer-reviewed articles) and developed a system with database indexes for efficiently identifying overlaps between any new PBS and the PBSs already in the database since such overlaps suggest plagiarism. The identified overlaps are then used locally with the SAVE_App to highlight the potentially plagiarized part of the original documents on the user's computer. For the non-private mode internet search, we break the document's contents into blocks of texts and search for each block on the internet using Google's API. The parts of the blocks that are found on the internet are then aligned to the document's contents by in-house dynamics programming such that the document's regions with 12 or more consecutive words matching contents on the internet are flagged for potential plagiarism.

English Abstract ii
Mandarin Chinese Abstract vi
Dedication ix
Acknowledgements x
Table of Contents xi
List of Figures xviii
List of Tables xxii

Chapter 1. Water Molecules Actively Facilitate DNA-Kinking Induced by a Sequence General DNA-Bending Protein Sac7d 1
1.1 Introduction 1
1.2 Methods 4
1.2.1 System Setup and Energy Minimization 4
1.2.2 Molecular Dynamics Simulations 5
1.2.3 Force Calculations 8
1.2.4 Grid Inhomogeneous Solvation Theory (GIST) 8
1.3 Results and Discussions 8
1.3.1 Sac7d Approach and Capture of dsDNA Traps Water Molecules in Interfacial Pockets 8
1.3.2 Catalytic Water Molecules Initializes dsDNA Kinking 10
1.3.3 Intercalation of Sac7d's V26 and M29 into Base Pairs Enhances the dsDNA Kinking 15
1.3.4 MD-Obtained Forces from the Catalytic Water Molecules, V26, and M29 are Consistent with the Findings from Experiments 16
1.3.5 dsDNA is Never Kinked in the Absence of the Water Molecules 17
1.3.6 Removal of the Explicit Water Molecules Reverses the dsDNA Kinking 18
1.3.7 dsDNA Kinking by Sac7d May Not be Totally Nonspecific 19
1.4 Conclusions 21
1.5 Supplementary Information 23
1.5.1 Obtaining Energy Landscapes for the pre-complex to mature transition. 27
1.5.2 Finding the Lowest-Energy Paths Connecting the Bound and Bent States 28
1.5 References 40

Chapter 2. TDP-43 RNA Binding Motif Binds and Unwinds Double-Stranded DNA by Leveraging Guanine-Binding Specificity 49
2.1 Introduction 49
2.2 Material and Methods 51
2.2.1 Protein Purification and Sample Preparation 51
2.2.2 Fluorescence Anisotropy 52
2.2.3 F-EMSA for dsDNA/dsRNA Unwinding 52
2.2.4 Fluorescence Recovery for Time-course Unwinding Assay 53
2.2.5 Preparation of the Initial 3D Structures 53
2.2.6 Creation of Input Files for MD Simulations 54
2.2.7 Energy Minimization 55
2.2.8 Equilibration and Production Run 55
2.2.9 Binding Gibbs free Energy Change Calculations Using MM/PBSA 55
2.2.10 ABMD Simulations 56
2.2.11 Protein-Nucleotide Docking 56
2.2.12 Conservation Score 57
2.3 Results 57
2.3.1 RRM1 Binds TG/UG Repeats Better than its Structural Homolog, RRM2 57
2.3.2 RRM Proteins Bind RNA Better than ssDNA due to their Selectivity for RNA Backbone Rather than the Uracil/Thymine Difference 58
2.3.3 Guanine Contributes More Binding Affinity than Thymine and Uracil 59
2.3.4 RRM1 Better Binds ssDNA/RNA than RRM2 with its Positive and Aromatic Residues 60
2.3.4 Mutation on RRM2 makes Binding Affinity Better 61
2.3.5 RRM1 but not RRM2 Unwinds and Separates Double-Stranded DNA of TG-Repeats 62
2.3.6 Adaptively Biased MD (ABMD) Simulations Reveal that RRM1 can Better Facilitates the Opening of ds(TG)6 than RRM2 63
2.3.7 Partial Overlap of ssDNA/RNA and dsDNA Binding Sites Together with Sequence Conservation Suggesting the Functional Evolution of RRMs 64
2.4 Discussion 65
2.4.1 How Strong a ssDNA Binding Affinity Would Imply a Potential ATP-Independent Helicase Function 65
2.4.2 The Importance of Guanine Binding by RNA Chaperones 66
2.4.3 Possible Reasons for RNA Chaperones to Comprise both Strong and Weak RRMs 66
2.5 Tables and Figures Legends 68
2.6 Supplementary Data 80
2.7 References 105

Chapter 3. Resolution-Exchanged Structural Modeling and Simulations Jointly Unravel That Subunit Rolling Underlies the Mechanism of Programmed Ribosomal Frameshifting 111
3.1 Introduction 111
3.2 Results 116
3.2.1 ANM captures the intrinsic dynamics of ribosomal body rotation (ratcheting), L1 stalk closing and local conformational changes that were observed by X-ray crystallography, FRET and cryo-EM 116
3.2.2 Cryo-EM fitting locates the PK at the mRNA entrance and the forces calculated for PK at the “+12 position” reveal experimentally verified active site of ribosomal helicase 118
3.2.3 LRT predicts rolling motion of the 30S subunit upon PK binding, which is consistent with FRET-identified separation of labelled dye-pairs 122
3.2.4 Predicted A/P-tRNA distortion caused by rolling resembles observed A/P-tRNA distortion by cryo-EM 125
3.2.5 Distorted A/P-tRNA exhibits spontaneous dissociation and slippage (-1 frameshifting) on mRNA in the hTR-PK case but not C3GU (the negative control) 127
3.3 Discussion and Conclusions 130
3.4 Methods 133
3.4.1 Linear Response Theory 133
3.5 Supplementary Methods 134
The Supplementary Methods section comprises topics related to (1) linear response theory (LRT), (2) structure modeling, (3) MD simulations and (4) anisotropic network model (ANM). 134
3.5.1 LRT, the time-independent formulation 135
3.5.2 Structure Modeling 138
3.5.3 Molecular Dynamics (MD) Simulations 143
3.5.4 Anisotropic Network Model (ANM) 148
3.6 Supplementary Figures and Tables 155
3.7 Supplementary Movie Legends 166
3.8 References 167

Chapter 4. Data-Driven Design of Therapeutic Peptides 181
4.1 Introduction 181
4.2 Methods 183
4.2.1 Extraction of Helical Peptide Sequences from the Protein Data Bank (PDB) 183
4.2.2 Creation of TP-DB 183
4.2.3 Querying the TP-DB 186
4.2.4 The TP-DB 187
4.2.5 Ranking of the Helical Peptides 187
4.2.6 Applications of the TP-DB for Developing a Peptide that Blocks Sgo2 from interacting with PP2A 188
4.3 Results and Discussions 191
4.3.1 The Database, Search Engine Itself and Search Results 191
4.3.2 Α Helical Peptide Blocker of Tumorgenic PPI 194
4.3.3 α-Helical Antimicrobial Peptide (AMP) Design 203
4.4 References 208

Chapter 5. SAVE - A Plagiarism Detection Tool with Enhanced Privacy Protection 211
5.1 Introduction 211
5.2 Existing Plagiarism Detection Software/Platform 214
5.2.1 Keyword-Based Plagiarism Detection Platforms 214
5.2.2 Text-Alignment-Based Plagiarism Detection Platforms 215
5.2.3 Stylometry-Based Plagiarism Detection 217
5.2.4 Others 217
5.3 Methods used in SAVE 218
5.3.1 Extraction of Text from Documents 218
5.3.2 Removal of References (done by my colleague, Mr. Yuan-Yu Chang) 218
5.3.3 Removal of Redundant/Common Words and Punctuation Marks (done by my colleague, Mr. Yuan-Yu Chang) 219
5.3.4 Encoding Human Readable Texts into Pseudo-Biological Sequences (PBS) 220
5.3.5 Pairwise Comparison of Two or More Documents 222
5.3.6 Detection of Plagiarism of WWW Contents/Internet Search (done by my colleague, Mr. Yuan-Yu Chang) 225
5.3.7 Detection of Plagiarism by Internet Search with Full Privacy 225
5.4 Usage and Results 231
5.4.1 Optional SAVE Desktop Application for Pairwise and Internet Search in Private Mode 231
5.4.2. Using SAVE in a Non-Private Mode (Regular Mode) 233
5.4.3 Using SAVE while Keeping your Data Private 239
5.5 References 247

List of Publications 249
Published Peer-Reviewed Papers 249
Submitted Manuscripts/Manuscripts in Preparation 250
Published Book Chapter 251

Aduri, R., Psciuk, B.T., Saro, P., Taniga, H., Schlegel, H.B., and SantaLucia, J. (2007). AMBER force field parameters for the naturally occurring modified nucleosides in RNA. J. Chem. Theory Comput. 3, 1464–1475.
Agback, P., Baumann, H., Knapp, S., Ladenstein, R., and Härd, T. (1998). Architecture of nonspecific protein--DNA interactions in the Sso7d--DNA complex. Nat. Struct. Mol. Biol. 5, 579.
Agirrezabala, X., Schreiner, E., Trabuco, L.G., Lei, J., Ortiz-Meoz, R.F., Schulten, K., Green, R., and Frank, J. (2011). Structural insights into cognate versus near-cognate discrimination during decoding. EMBO J. 30, 1497–1507.
Agirrezabala, X., Samatova, E., Klimova, M., Zamora, M., Gil-Carton, D., Rodnina, M. V, and Valle, M. (2017). Ribosome rearrangements at the onset of translational bypassing. Sci. Adv. 3, e1700147.
Aida, M., and Nagata, C. (1986). An ab initio molecular orbital study on the stacking interaction between nucleic acid bases: Dependence on the sequence and relation to the conformation. Int. J. Quantum Chem. 29, 1253–1261.
Amemiya, T., Koike, R., Kidera, A., and Ota, M. (2011). PSCDB: a database for protein structural change upon ligand binding. Nucleic Acids Res. 40, D554--D558.
Ashkenazy, H., Abadi, S., Martz, E., Chay, O., Mayrose, I., Pupko, T., and Ben-Tal, N. (2016). ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res. 44, W344--W350.
Atilgan, A.R., Durell, S.R., Jernigan, R.L., Demirel, M.C., Keskin, O., and Bahar, I. (2001). Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys. J. 80, 505–515.
Atkins, J.F., Loughran, G., Bhatt, P.R., Firth, A.E., and Baranov, P. V (2016). Ribosomal frameshifting and transcriptional slippage: from genetic steganography and cryptography to adventitious use. Nucleic Acids Res. 44, 7007–7078.
Babin, V., Roland, C., and Sagui, C. (2008). Adaptively biased molecular dynamics for free energy calculations. J. Chem. Phys. 128, 134101.
Bahar, I., Atilgan, A.R., Demirel, M.C., and Erman, B. (1998). Vibrational dynamics of folded proteins: significance of slow and fast motions in relation to function and stability. Phys. Rev. Lett. 80, 2733.
Bahar, I., Lezon, T.R., Yang, L.-W., and Eyal, E. (2010). Global dynamics of proteins: bridging between structure and function. Annu. Rev. Biophys. 39, 23.
de Bakker, P.I.W., HuÈnenberger, P.H., and McCammon, J.A. (1999). Molecular dynamics simulations of the hyperthermophilic protein sac7d from Sulfolobus acidocaldarius: contribution of salt bridges to thermostability1. J. Mol. Biol. 285, 1811–1830.
Banerjee, A., Neiner, T., Tripp, P., and Albers, S.-V. (2013). Insights into subunit interactions in the Sulfolobus acidocaldarius archaellum cytoplasmic complex. FEBS J. 280, 6141–6149.
Bassett, A., Cooper, S., Wu, C., and Travers, A. (2009). The folding and unfolding of eukaryotic chromatin. Curr. Opin. Genet. Dev. 19, 159–165.
Berendsen, H.J.C., Postma, J.P.M., van Gunsteren, W.F., DiNola, A., and Haak, J.R. (1984). Molecular dynamics with coupling to an external bath. J. Chem. Phys. 81, 3684–3690.
Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N., and Bourne, P.E. (2000). The Protein Data Bank. Nucleic Acids Res. 28, 235–242.
Bernander, R., and Poplawski, A. (1997). Cell cycle characteristics of thermophilic archaea. J. Bacteriol. 179, 4963–4969.
Bewley, C.A., Gronenborn, A.M., and Clore, G.M. (1998). Minor groove-binding architectural proteins: structure, function, and DNA recognition 1. Annu. Rev. Biophys. Biomol. Struct. 27, 105–131.
Biasini, M., Bienert, S., Waterhouse, A., Arnold, K., Studer, G., Schmidt, T., Kiefer, F., Cassarino, T.G., Bertoni, M., Bordoli, L., et al. (2014). SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information. Nucleic Acids Res. gku340.
Blaha, G., Stanley, R.E., and Steitz, T.A. (2009). Formation of the first peptide bond: the structure of EF-P bound to the 70S ribosome. Science (80-. ). 325, 966–970.
Bocharov, E. V, Sobol, A.G., Pavlov, K. V, Korzhnev, D.M., Jaravine, V.A., Gudkov, A.T., and Arseniev, A.S. (2004). From structure and dynamics of protein L7/L12 to molecular switching in ribosome. J. Biol. Chem. 279, 17697–17706.
Borovinskaya, M.A., Shoji, S., Holton, J.M., Fredrick, K., and Cate, J.H.D. (2007). A steric block in translation caused by the antibiotic spectinomycin. ACS Chem. Biol. 2, 545–552.
Bowen, M.E., Weninger, K., Ernst, J., Chu, S., and Brunger, A.T. (2005). Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex. Biophys. J. 89, 690–702.
Brierley, I. (1995). Ribosomal frameshifting on viral RNAs. J. Gen. Virol. 76, 1885–1892.
Brierley, I., Jenner, A.J., and Inglis, S.C. (1992). Mutational analysis of the “slippery-sequence” component of a coronavirus ribosomal frameshifting signal. J. Mol. Biol. 227, 463–479.
Brilot, A.F., Korostelev, A.A., Ermolenko, D.N., and Grigorieff, N. (2013). Structure of the ribosome with elongation factor G trapped in the pretranslocation state. Proc. Natl. Acad. Sci. 110, 20994–20999.
Brooks, B., and Karplus, M. (1983). Harmonic dynamics of proteins: normal modes and fluctuations in bovine pancreatic trypsin inhibitor. Proc. Natl. Acad. Sci. 80, 6571–6575.
Budkevich, T. V, Giesebrecht, J., Behrmann, E., Loerke, J., Ramrath, D.J.F., Mielke, T., Ismer, J., Hildebrand, P.W., Tung, C.-S., Nierhaus, K.H., et al. (2014). Regulation of the mammalian elongation cycle by subunit rolling: a eukaryotic-specific ribosome rearrangement. Cell 158, 121–131.
Bunch, H. (2016). Role of genome guardian proteins in transcriptional elongation. FEBS Lett. 590, 1064–1075.
Case, D.A., Cheatham, T.E., Darden, T., Gohlke, H., Luo, R., Merz, K.M., Onufriev, A., Simmerling, C., Wang, B., and Woods, R.J. (2005). The Amber biomolecular simulation programs. J. Comput. Chem. 26, 1668–1688.
Case, D.A., Babin, V., Berryman, J., Betz, R.M., Cai, Q., Cerutti, D.S., Cheatham Iii, T.E., Darden, T.A., Duke, R.E., Gohlke, H., et al. (2014). Amber 14.
Chan, J., Lin, H.-R., Takemura, K., Chang, K.-C., Chang, Y.-Y., Joti, Y., Kitao, A., and Yang, L.-W. (2018). An efficient timer and sizer of protein motions reveals the time scales of functional dynamics in the ribosome. BioRxiv.
Chang, K.-C., Wen, J.-D., and Yang, L.-W. (2015). Functional importance of mobile ribosomal proteins. Biomed Res. Int. 2015.
Chargaff, E., Lipshitz, R., and Green, C. (1952). Composition of the desoxypentose nucleic acids of four genera of sea-urchin. J Biol Chem 195, 155–160.
Chen, C.-Y., Ko, T.-P., Lin, T.-W., Chou, C.-C., Chen, C.-J., and Wang, A.H.-J. (2005). Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d. Nucleic Acids Res. 33, 430–438.
Chen, C., Esadze, A., Zandarashvili, L., Nguyen, D., Pettitt, B.M., and Iwahara, J. (2015). Dynamic equilibria of short-range electrostatic interactions at molecular interfaces of protein--DNA complexes. J. Phys. Chem. Lett. 6, 2733–2737.
Chen, G., Chang, K.-Y., Chou, M.-Y., Bustamante, C., and Tinoco, I. (2009). Triplex structures in an RNA pseudoknot enhance mechanical stability and increase efficiency of--1 ribosomal frameshifting. Proc. Natl. Acad. Sci. 106, 12706–12711.
Chen, J., Petrov, A., Johansson, M., Tsai, A., O’Leary, S.E., and Puglisi, J.D. (2014). Dynamic pathways of-1 translational frameshifting. Nature 512, 328–332.
Chen, Y.-T., Chang, K.-C., Hu, H.-T., Chen, Y.-L., Lin, Y.-H., Hsu, C.-F., Chang, C.-F., Chang, K.-Y., and Wen, J.-D. (2017). Coordination among tertiary base pairs results in an efficient frameshift-stimulating RNA pseudoknot. Nucleic Acids Res. 45, 6011–6022.
Choli, T., Wittmann-Liebold, B., and Reinhardt, R. (1988). Microsequence analysis of DNA-binding proteins 7a, 7b, and 7e from the archaebacterium Sulfolobus acidocaldarius. J. Biol. Chem. 263, 7087–7093.
Chou, M.-Y., and Chang, K.-Y. (2009). An intermolecular RNA triplex provides insight into structural determinants for the pseudoknot stimulator of- 1 ribosomal frameshifting. Nucleic Acids Res. gkp1107.
Cornish, P. V, Ermolenko, D.N., Noller, H.F., and Ha, T. (2008). Spontaneous intersubunit rotation in single ribosomes. Mol. Cell 30, 578–588.
Cornish, P. V, Ermolenko, D.N., Staple, D.W., Hoang, L., Hickerson, R.P., Noller, H.F., and Ha, T. (2009). Following movement of the L1 stalk between three functional states in single ribosomes. Proc. Natl. Acad. Sci. 106, 2571–2576.
Coulombe, B., and Burton, Z.F. (1999). DNA bending and wrapping around RNA polymerase: a “revolutionary” model describing transcriptional mechanisms. Microbiol. Mol. Biol. Rev. 63, 457–478.
Crooks, G.E., Hon, G., Chandonia, J.-M., and Brenner, S.E. (2004). WebLogo: a sequence logo generator. Genome Res. 14, 1188–1190.
Darden, T., York, D., and Pedersen, L. (1993). Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. J. Chem. Phys. 98, 10089–10092.
Darve, E., and Pohorille, A. (2001). Calculating free energies using average force. J. Chem. Phys. 115, 9169–9183.
Davydov, I.I., Wohlgemuth, I., Artamonova, I.I., Urlaub, H., Tonevitsky, A.G., and Rodnina, M. V (2013). Evolution of the protein stoichiometry in the L12 stalk of bacterial and organellar ribosomes. Nat. Commun. 4, 1387.
DeWilde, M., and Wittmann-Liebold, B. (1973). Localization of the amino-acid exchange in protein S5 from an Escherichia coli mutant resistant to spectinomycin. Mol. Gen. Genet. MGG 127, 273–276.
Diaconu, M., Kothe, U., Schlünzen, F., Fischer, N., Harms, J.M., Tonevitsky, A.G., Stark, H., Rodnina, M. V, and Wahl, M.C. (2005). Structural basis for the function of the ribosomal L7/12 stalk in factor binding and GTPase activation. Cell 121, 991–1004.
Dijkstra, E.W. (1959). A note on two problems in connexion with graphs. Numer. Math. 1, 269–271.
Duggin, I.G., McCallum, S.A., and Bell, S.D. (2008). Chromosome replication dynamics in the archaeon Sulfolobus acidocaldarius. Proc. Natl. Acad. Sci.
Essiz, S.G., and Coalson, R.D. (2009). Dynamic linear response theory for conformational relaxation of proteins. J. Phys. Chem. B 113, 10859–10869.
Fei, J., Bronson, J.E., Hofman, J.M., Srinivas, R.L., Wiggins, C.H., and Gonzalez, R.L. (2009). Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movements during translation. Proc. Natl. Acad. Sci. 106, 15702–15707.
Felsenfeld, G., and Groudine, M. (2003). Controlling the double helix. Nature 421, 448.
Fischer, N., Konevega, A.L., Wintermeyer, W., Rodnina, M. V, and Stark, H. (2010). Ribosome dynamics and tRNA movement by time-resolved electron cryomicroscopy. Nature 466, 329–333.
Fischer, N., Neumann, P., Bock, L. V, Maracci, C., Wang, Z., Paleskava, A., Konevega, A.L., Schröder, G.F., Grubmüller, H., Ficner, R., et al. (2016). The pathway to GTPase activation of elongation factor SelB on the ribosome. Nature 540, 80.
Flanagan, J.F., Namy, O., Brierley, I., and Gilbert, R.J.C. (2010). Direct observation of distinct A/P hybrid-state tRNAs in translocating ribosomes. Structure 18, 257–264.
Flory, P., Volkenstein, M., and others (1969). Statistical mechanics of chain molecules.
Flynn, R.L., and Zou, L. (2010). Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians. Crit. Rev. Biochem. Mol. Biol. 45, 266–275.
Fredman, M.L., and Tarjan, R.E. (1987). Fibonacci heaps and their uses in improved network optimization algorithms. J. ACM 34, 596–615.
Friedman, R.A., and Honig, B. (1995). A free energy analysis of nucleic acid base stacking in aqueous solution. Biophys. J. 69, 1528.
Fu, H.-W., and Kuo, T.-Y. (2017). Methods for diagnosing and treating Helicobacter pylori infection.
Gao, Y.-G., Su, S.-Y., Robinson, H., Padmanabhan, S., Lim, L., McCrary, B.S., Edmondson, S.P., Shriver, J.W., and Wang, A.H.-J. (1998). The crystal structure of the hyperthermophile chromosomal protein Sso7d bound to DNA. Nat. Struct. Mol. Biol. 5, 782–786.
Gao, Y.-G., Selmer, M., Dunham, C.M., Weixlbaumer, A., Kelley, A.C., and Ramakrishnan, V. (2009). The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science (80-. ). 326, 694–699.
Garcia, H.G., Grayson, P., Han, L., Inamdar, M., Kondev, J., Nelson, P.C., Phillips, R., Widom, J., and Wiggins, P.A. (2007). Biological consequences of tightly bent DNA: the other life of a macromolecular celebrity. Biopolym. Orig. Res. Biomol. 85, 115–130.
Grogan, D.W. (1996). Exchange of genetic markers at extremely high temperatures in the archaeon Sulfolobus acidocaldarius. J. Bacteriol. 178, 3207–3211.
Guagliardi, A., Napoli, A., Rossi, M., and Ciaramella, M. (1997). Annealing of complementary DNA strands above the melting point of the duplex promoted by an archaeal protein1. J. Mol. Biol. 267, 841–848.
Guex, N., and Peitsch, M.C. (1997). SWISS-MODEL and the Swiss-Pdb Viewer: an environment for comparative protein modeling. Electrophoresis 18, 2714–2723.
Haliloglu, T., Bahar, I., and Erman, B. (1997). Gaussian dynamics of folded proteins. Phys. Rev. Lett. 79, 3090.
Hopkins, C.W., Le Grand, S., Walker, R.C., and Roitberg, A.E. (2015). Long-time-step molecular dynamics through hydrogen mass repartitioning. J. Chem. Theory Comput. 11, 1864–1874.
Hu, H.-T., Cho, C.-P., Lin, Y.-H., and Chang, K.-Y. (2015). A general strategy to inhibiting viral- 1 frameshifting based on upstream attenuation duplex formation. Nucleic Acids Res. gkv1307.
Huang, J., and MacKerell, A.D. (2013). CHARMM36 all-atom additive protein force field: Validation based on comparison to NMR data. J. Comput. Chem. 34, 2135–2145.
Husain, I., Griffith, J., and Sancar, A. (1988). Thymine dimers bend DNA. Proc. Natl. Acad. Sci. 85, 2558–2562.
Ikeguchi, M., Ueno, J., Sato, M., and Kidera, A. (2005). Protein structural change upon ligand binding: linear response theory. Phys. Rev. Lett. 94, 78102.
Ilag, L.L., Videler, H., McKay, A.R., Sobott, F., Fucini, P., Nierhaus, K.H., and Robinson, C. V (2005). Heptameric (L12) 6/L10 rather than canonical pentameric complexes are found by tandem MS of intact ribosomes from thermophilic bacteria. Proc. Natl. Acad. Sci. U. S. A. 102, 8192–8197.
Ishii, Y., Yoshida, T., Funatsu, T., Wazawa, T., and Yanagida, T. (1999). Fluorescence resonance energy transfer between single fluorophores attached to a coiled-coil protein in aqueous solution. Chem. Phys. 247, 163–173.
Ivani, I., Dans, P.D., Noy, A., Pérez, A., Faustino, I., Hospital, A., Walther, J., Andrio, P., Goñi, R., Balaceanu, A., et al. (2016). Parmbsc1: a refined force field for DNA simulations. Nat. Methods 13, 55.
Jacob, F. (1977). Evolution and tinkering. Science (80-. ). 196, 1161–1166.
Jenner, L.B., Demeshkina, N., Yusupova, G., and Yusupov, M. (2010). Structural aspects of messenger RNA reading frame maintenance by the ribosome. Nat. Struct. Mol. Biol. 17, 555–560.
Joung, I.S., and Cheatham III, T.E. (2008). Determination of alkali and halide monovalent ion parameters for use in explicitly solvated biomolecular simulations. J. Phys. Chem. B 112, 9020–9041.
Kim, J., Klooster, S., and Shapiro, D.J. (1995). Intrinsically bent DNA in a eukaryotic transcription factor recognition sequence potentiates transcription activation. J. Biol. Chem. 270, 1282–1288.
Kim, K.K., Hung, L.-W., Yokota, H., Kim, R., and Kim, S.-H. (1998). Crystal structures of eukaryotic translation initiation factor 5A from Methanococcus jannaschii at 1.8 Åresolution. Proc. Natl. Acad. Sci. 95, 10419–10424.
Kim, N.-K., Zhang, Q., Zhou, J., Theimer, C.A., Peterson, R.D., and Feigon, J. (2008). Solution structure and dynamics of the wild-type pseudoknot of human telomerase RNA. J. Mol. Biol. 384, 1249–1261.
Kirthi, N., Roy-Chaudhuri, B., Kelley, T., and Culver, G.M. (2006). A novel single amino acid change in small subunit ribosomal protein S5 has profound effects on translational fidelity. Rna.
Ko, T.-P., Chu, H.-M., Chen, C.-Y., Chou, C.-C., and Wang, A.-J. (2004). Structures of the hyperthermophilic chromosomal protein Sac7d in complex with DNA decamers. Acta Crystallogr. Sect. D Biol. Crystallogr. 60, 1381–1387.
Kollman, P.A., Massova, I., Reyes, C., Kuhn, B., Huo, S., Chong, L., Lee, M., Lee, T., Duan, Y., Wang, W., et al. (2000). Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models. Acc. Chem. Res. 33, 889–897.
Kondrashov, D.A., Cui, Q., and Phillips, G.N. (2006). Optimization and evaluation of a coarse-grained model of protein motion using x-ray crystal data. Biophys. J. 91, 2760–2767.
Korostelev, A., Trakhanov, S., Laurberg, M., and Noller, H.F. (2006). Crystal structure of a 70S ribosome-tRNA complex reveals functional interactions and rearrangements. Cell 126, 1065–1077.
Kurkcuoglu, O., Doruker, P., Sen, T.Z., Kloczkowski, A., and Jernigan, R.L. (2008). The ribosome structure controls and directs mRNA entry, translocation and exit dynamics. Phys. Biol. 5, 46005.
Larsen, B., Gesteland, R.F., and Atkins, J.F. (1997). Structural probing and mutagenic analysis of the stem-loop required for Escherichia coli dnaX ribosomal frameshifting: programmed efficiency of 50% 1. J. Mol. Biol. 271, 47–60.
Li, D.-W., and Brüschweiler, R. (2009). All-atom contact model for understanding protein dynamics from crystallographic B-factors. Biophys. J. 96, 3074–3081.
Li, H., Chang, Y.-Y., Lee, J.Y., Bahar, I., and Yang, L.-W. (2017). DynOmics: dynamics of structural proteome and beyond. Nucleic Acids Res. 45, W374--W380.
Loncharich, R.J., Brooks, B.R., and Pastor, R.W. (1992). Langevin dynamics of peptides: The frictional dependence of isomerization rates of N-acetylalanyl-N′-methylamide. Biopolym. Orig. Res. Biomol. 32, 523–535.
Love, J.J., Li, X., Case, D.A., Giese, K., Grosschedl, R., and Wright, P.E. (1995). Structural basis for DNA bending by the architectural transcription factor LEF-1. Nature 376, 791.
Lu, X.-J., and Olson, W.K. (2003). 3DNA: a software package for the analysis, rebuilding and visualization of three-dimensional nucleic acid structures. Nucleic Acids Res. 31, 5108–5121.
Lu, M., Poon, B., and Ma, J. (2006). A new method for coarse-grained elastic normal-mode analysis. J. Chem. Theory Comput. 2, 464–471.
Luke, K.A., Higgins, C.L., and Wittung-Stafshede, P. (2007). Thermodynamic stability and folding of proteins from hyperthermophilic organisms. FEBS J. 274, 4023–4033.
Macke, T.J., and Case, D.A. (1998). Modeling unusual nucleic acid structures. (ACS Publications), p.
Maier, J.A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K.E., and Simmerling, C. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. J. Chem. Theory Comput. 11, 3696–3713.
Maréchal, A., and Zou, L. (2015). RPA-coated single-stranded DNA as a platform for post-translational modifications in the DNA damage response. Cell Res. 25, 9.
Marshall, R.A., Dorywalska, M., and Puglisi, J.D. (2008). Irreversible chemical steps control intersubunit dynamics during translation. Proc. Natl. Acad. Sci. 105, 15364–15369.
Matsumoto, A., and Ishida, H. (2009). Global conformational changes of ribosome observed by normal mode fitting for 3D Cryo-EM structures. Structure 17, 1605–1613.
Melnikov, S., Ben-Shem, A., de Loubresse, N.G., Jenner, L., Yusupova, G., and Yusupov, M. (2012). One core, two shells: bacterial and eukaryotic ribosomes. Nat. Struct. Mol. Biol. 19, 560–567.
Ming, D., and Wall, M.E. (2005). Allostery in a coarse-grained model of protein dynamics. Phys. Rev. Lett. 95, 198103.
Mohan, S., Donohue, J.P., and Noller, H.F. (2014). Molecular mechanics of 30S subunit head rotation. Proc. Natl. Acad. Sci. 111, 13325–13330.
Mukherjee, S., and Zhang, Y. (2009). MM-align: a quick algorithm for aligning multiple-chain protein complex structures using iterative dynamic programming. Nucleic Acids Res. 37, e83--e83.
Murphy IV, F. V, and Churchill, M.E.A. (2000). Nonsequence-specific DNA recognition: a structural perspective. Structure 8, R83--R89.
Nakagawa, H., Yonetani, Y., Nakajima, K., Ohira-Kawamura, S., Kikuchi, T., Inamura, Y., Kataoka, M., and Kono, H. (2014). Local dynamics coupled to hydration water determines DNA-sequence-dependent deformability. Phys. Rev. E 90, 22723.
Namy, O., Moran, S.J., Stuart, D.I., Gilbert, R.J.C., and Brierley, I. (2006). A mechanical explanation of RNA pseudoknot function in programmed ribosomal frameshifting. Nature 441, 244–247.
Napthine, S., Liphardt, J., Bloys, A., Routledge, S., and Brierley, I. (1999). The role of RNA pseudoknot stem 1 length in the promotion of efficient- 1 ribosomal frameshifting. J. Mol. Biol. 288, 305–320.
Nguyen, C.N., Kurtzman Young, T., and Gilson, M.K. (2012). Grid inhomogeneous solvation theory: hydration structure and thermodynamics of the miniature receptor cucurbit [7] uril. J. Chem. Phys. 137, 44101.
Nguyen, H., Roe, D.R., and Simmerling, C. (2013). Improved generalized born solvent model parameters for protein simulations. J. Chem. Theory Comput. 9, 2020–2034.
Noeske, J., Wasserman, M.R., Terry, D.S., Altman, R.B., Blanchard, S.C., and Cate, J.H.D. (2015). High-resolution structure of the Escherichia coli ribosome. Nat. Struct. Mol. Biol. 22, 336–341.
Pabo, C.O., and Sauer, R.T. (1992). Transcription factors: structural families and principles of DNA recognition. Annu. Rev. Biochem. 61, 1053–1095.
Parker, J. (1989). Errors and alternatives in reading the universal genetic code. Microbiol. Rev. 53, 273.
Pastor, R.W., Brooks, B.R., and Szabo, A. (1988). An analysis of the accuracy of Langevin and molecular dynamics algorithms. Mol. Phys. 65, 1409–1419.
Pearlman, D.A., Case, D.A., Caldwell, J.W., Ross, W.S., Cheatham, T.E., DeBolt, S., Ferguson, D., Seibel, G., and Kollman, P. (1995). AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Comput. Phys. Commun. 91, 1–41.
Pérez, A., Marchán, I., Svozil, D., Sponer, J., Cheatham III, T.E., Laughton, C.A., and Orozco, M. (2007). Refinement of the AMBER force field for nucleic acids: improving the description of $α$/$γ$ conformers. Biophys. J. 92, 3817–3829.
Phillips, J.C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., Chipot, C., Skeel, R.D., Kale, L., and Schulten, K. (2005). Scalable molecular dynamics with NAMD. J. Comput. Chem. 26, 1781–1802.
Protozanova, E., Yakovchuk, P., and Frank-Kamenetskii, M.D. (2004). Stacked--unstacked equilibrium at the nick site of DNA. J. Mol. Biol. 342, 775–785.
Qin, P., Yu, D., Zuo, X., and Cornish, P. V (2014). Structured mRNA induces the ribosome into a hyper-rotated state. EMBO Rep.
Qu, X., Wen, J.-D., Lancaster, L., Noller, H.F., Bustamante, C., and Tinoco, I. (2011). The ribosome uses two active mechanisms to unwind messenger RNA during translation. Nature 475, 118–121.
Razvi, A., and Scholtz, J.M. (2006). Lessons in stability from thermophilic proteins. Protein Sci. 15, 1569–1578.
Robinson, H., Gao, Y.-G., McCrary, B.S., Edmondson, S.P., Shriver, J.W., and Wang, A.H.-J. (1998). The hyperthermophile chromosomal protein Sac7d sharply kinks DNA. Nature 392, 202–205.
Roe, D.R., and Cheatham III, T.E. (2013). PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9, 3084–3095.
Rohs, R., West, S.M., Sosinsky, A., Liu, P., Mann, R.S., and Honig, B. (2009). The role of DNA shape in protein--DNA recognition. Nature 461, 1248–1253.
Roy, A., Kucukural, A., and Zhang, Y. (2010). I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc. 5, 725–738.
Salomon-Ferrer, R., Case, D. a., and Walker, R.C. (2013a). An overview of the Amber biomolecular simulation package. Wiley Interdiscip. Rev. Comput. Mol. Sci. 3, 198–210.
Salomon-Ferrer, R., Götz, A.W., Poole, D., Le Grand, S., and Walker, R.C. (2013b). Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. Explicit solvent particle mesh Ewald. J. Chem. Theory Comput. 9, 3878–3888.
Sampathi, S., and Chai, W. (2011). Telomere replication: poised but puzzling. J. Cell. Mol. Med. 15, 3–13.
Sanbonmatsu, K.Y. (2012). Computational studies of molecular machines: the ribosome. Curr. Opin. Struct. Biol. 22, 168–174.
Sandmann, A., and Sticht, H. (2018). Probing the role of intercalating protein sidechains for kink formation in DNA. PLoS One 13, e0192605.
Schmeing, T.M., Voorhees, R.M., Kelley, A.C., Gao, Y.-G., Murphy, F. V, Weir, J.R., and Ramakrishnan, V. (2009). The crystal structure of the ribosome bound to EF-Tu and aminoacyl-tRNA. Science (80-. ). 326, 688–694.
Schoepp-Cothenet, B., Schütz, M., Baymann, F., Brugna, M., Nitschke, W., Myllykallio, H., and Schmidt, C. (2001). The membrane-extrinsic domain of cytochrome b 558/566 from the Archaeon Sulfolobus acidocaldarius performs pivoting movements with respect to the membrane surface. FEBS Lett. 487, 372–376.
Selmer, M., Dunham, C.M., Murphy, F. V, Weixlbaumer, A., Petry, S., Kelley, A.C., Weir, J.R., and Ramakrishnan, V. (2006). Structure of the 70S ribosome complexed with mRNA and tRNA. Science (80-. ). 313, 1935–1942.
Seno, Y., and Gō, N. (1990a). Deoxymyoglobin studied by the conformational normal mode analysis: II. The conformational change upon oxygenation. J. Mol. Biol. 216, 111–126.
Seno, Y., and Gō, N. (1990b). Deoxymyoglobin studied by the conformational normal mode analysis: I. Dynamics of globin and the heme-globin interaction. J. Mol. Biol. 216, 95–109.
Sinnokrot, M.O., Valeev, E.F., and Sherrill, C.D. (2002). Estimates of the ab initio limit for $π$-$π$ interactions: The benzene dimer. J. Am. Chem. Soc. 124, 10887–10893.
Slootstra, J.W., Kuperus, D., Plückthun, A., and Meloen, R.H. (1997). Identification of new tag sequences with differential and selective recognition properties for the anti-FLAG monoclonal antibodies M1, M2 and M5. Mol. Divers. 2, 156–164.
Smith, S.B., Cui, Y., and Bustamante, C. (1996). Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science (80-. ). 271, 795–799.
Stella, S., Cascio, D., and Johnson, R.C. (2010). The shape of the DNA minor groove directs binding by the DNA-bending protein Fis. Genes Dev. 24, 814–826.
Su, S., Gao, Y.-G., Robinson, H., Liaw, Y.-C., Edmondson, S.P., Shriver, J.W., and Wang, A.H.-J. (2000). Crystal structures of the chromosomal proteins Sso7d/Sac7d bound to DNA containing TG mismatched base-pairs. J. Mol. Biol. 303, 395–403.
Takyar, S., Hickerson, R.P., and Noller, H.F. (2005). mRNA helicase activity of the ribosome. Cell 120, 49–58.
Tama, F., Valle, M., Frank, J., and Brooks, C.L. (2003). Dynamic reorganization of the functionally active ribosome explored by normal mode analysis and cryo-electron microscopy. Proc. Natl. Acad. Sci. 100, 9319–9323.
Theimer, C.A., Blois, C.A., and Feigon, J. (2005). Structure of the human telomerase RNA pseudoknot reveals conserved tertiary interactions essential for function. Mol. Cell 17, 671–682.
Tolstorukov, M.Y., Jernigan, R.L., and Zhurkin, V.B. (2004). Protein--DNA hydrophobic recognition in the minor groove is facilitated by sugar switching. J. Mol. Biol. 337, 65–76.
Tolstorukov, M.Y., Colasanti, A. V, McCandlish, D.M., Olson, W.K., and Zhurkin, V.B. (2007). A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning. J. Mol. Biol. 371, 725–738.
Tourigny, D.S., Fernández, I.S., Kelley, A.C., and Ramakrishnan, V. (2013). Elongation factor G bound to the ribosome in an intermediate state of translocation. Science (80-. ). 340, 1235490.
Trabuco, L.G., Schreiner, E., Eargle, J., Cornish, P., Ha, T., Luthey-Schulten, Z., and Schulten, K. (2010). The role of L1 stalk--tRNA interaction in the ribosome elongation cycle. J. Mol. Biol. 402, 741–760.
Travers, A. (2005). DNA dynamics: bubble ‘n’flip for DNA cyclisation? Curr. Biol. 15, R377--R379.
Tsuchihashi, Z., and Brown, P.O. (1992). Sequence requirements for efficient translational frameshifting in the Escherichia coli dnaX gene and the role of an unstable interaction between tRNA (Lys) and an AAG lysine codon. Genes Dev. 6, 511–519.
Wang, C.-I., and Taylor, J.-S. (1991). Site-specific effect of thymine dimer formation on dAn. dTn tract bending and its biological implications. Proc. Natl. Acad. Sci. 88, 9072–9076.
Wang, F., and Landau, D.P. (2001). Efficient, multiple-range random walk algorithm to calculate the density of states. Phys. Rev. Lett. 86, 2050.
Wang, J., Hou, T., and Xu, X. (2006). Recent advances in free energy calculations with a combination of molecular mechanics and continuum models. Curr. Comput. Aided. Drug Des. 2, 287–306.
Wang, Y., Rader, A.J., Bahar, I., and Jernigan, R.L. (2004). Global ribosome motions revealed with elastic network model. J. Struct. Biol. 147, 302–314.
Weixlbaumer, A., Jin, H., Neubauer, C., Voorhees, R.M., Petry, S., Kelley, A.C., and Ramakrishnan, V. (2008). Insights into translational termination from the structure of RF2 bound to the ribosome. Science (80-. ). 322, 953–956.
Werner, M.H., Gronenborn, A.M., and Clore, G.M. (1996). Intercalation, DNA kinking, and the control of transcription. Science (80-. ). 271, 778–784.
Wriggers, W. (2010). Using Situs for the integration of multi-resolution structures. Biophys. Rev. 2, 21–27.
Xu, Z., Cetin, B., Anger, M., Cho, U.S., Helmhart, W., Nasmyth, K., and Xu, W. (2009). Structure and function of the PP2A-shugoshin interaction. Mol. Cell 35, 426–441.
Yamamoto, H., Unbehaun, A., Loerke, J., Behrmann, E., Collier, M., Bürger, J., Mielke, T., and Spahn, C.M.T. (2014). Structure of the mammalian 80S initiation complex with initiation factor 5B on HCV-IRES RNA. Nat. Struct. Mol. Biol. 21, 721–727.
Yamano, T., Nishimasu, H., Zetsche, B., Hirano, H., Slaymaker, I.M., Li, Y., Fedorova, I., Nakane, T., Makarova, K.S., Koonin, E. V, et al. (2016). Crystal structure of Cpf1 in complex with guide RNA and target DNA. Cell 165, 949–962.
Yan, S., Wen, J.-D., Bustamante, C., and Tinoco, I. (2015). Ribosome excursions during mRNA translocation mediate broad branching of frameshift pathways. Cell 160, 870–881.
Yang, L.-W. (2011). Models with energy penalty on interresidue rotation address insufficiencies of conventional elastic network models. Biophys. J. 100, 1784–1793.
Yang, L.-W., Kitao, A., Huang, B.-C., and Gō, N. (2014). Ligand-Induced Protein Responses and Mechanical Signal Propagation Described by Linear Response Theories. Biophys. J. 107, 1415–1425.
Yang, L.-W., Cheng, J.-W., Li, H.-C., Tsai, C.-Y., and Hui-Yuan, Y.U. (2017). Evaluation system for the efficacy of antimicrobial peptides and the use thereof.
Yang, L., Song, G., and Jernigan, R.L. (2009). Comparisons of experimental and computed protein anisotropic temperature factors. Proteins Struct. Funct. Bioinforma. 76, 164–175.
Yonetani, Y., and Kono, H. (2012). What determines water-bridge lifetimes at the surface of DNA? Insight from systematic molecular dynamics analysis of water kinetics for various DNA sequences. Biophys. Chem. 160, 54–61.
Yonetani, Y., and Kono, H. (2013). Dissociation free-energy profiles of specific and nonspecific DNA--protein complexes. J. Phys. Chem. B 117, 7535–7545.
Yonetani, Y., Maruyama, Y., Hirata, F., and Kono, H. (2008). Comparison of DNA hydration patterns obtained using two distinct computational methods, molecular dynamics simulation and three-dimensional reference interaction site model theory. J. Chem. Phys. 128, 05B608.
Yu, H.-Y., Huang, K.-C., Yip, B.-S., Tu, C.-H., Chen, H.-L., Cheng, H.-T., and Cheng, J.-W. (2010). Rational Design of Tryptophan-Rich Antimicrobial Peptides with Enhanced Antimicrobial Activities and Specificities. Chembiochem 11, 2273–2282.
Yuann, J.-M.P., Tseng, W.-H., Lin, H.-Y., and Hou, M.-H. (2012). The effects of loop size on Sac7d-hairpin DNA interactions. Biochim. Biophys. Acta (BBA)-Proteins Proteomics 1824, 1009–1015.
Yusupova, G., Jenner, L., Rees, B., Moras, D., and Yusupov, M. (2006). Structural basis for messenger RNA movement on the ribosome. Nature 444, 391–394.
Zhang, J., Pan, X., Yan, K., Sun, S., Gao, N., and Sui, S.-F. (2015). Mechanisms of ribosome stalling by SecM at multiple elongation steps. Elife 4, e09684.
Zhang, Y., Hong, S., Ruangprasert, A., Skiniotis, G., and Dunham, C.M. (2018). Alternative Mode of E-Site tRNA Binding in the Presence of a Downstream mRNA Stem Loop at the Entrance Channel. Structure 26, 437–445.
Zhang, Z., Miller, W., Schäffer, A.A., Madden, T.L., Lipman, D.J., Koonin, E. V, and Altschul, S.F. (1998). Protein sequence similarity searches using patterns as seeds. Nucleic Acids Res. 26, 3986–3990.
Zimmermann, M.T., Jia, K., and Jernigan, R.L. (2016). Ribosome mechanics informs about mechanism. J. Mol. Biol. 428, 802–810.