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Biochemistry 53, 7283\u20137296 (2014).","journal-title":"Biochemistry"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1073\/pnas.0610202104","article-title":"Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding","volume":"104","author":"Young T","year":"2007","unstructured":"T Young, R Abel, B Kim, BJ Berne, RA Friesner, Motifs for molecular recognition exploiting hydrophobic enclosure in protein-ligand binding. Proc Natl Acad Sci USA 104, 808\u2013813 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1002\/prot.24012","article-title":"Validating the vitality strategy for fighting drug resistance","volume":"80","author":"Singh N","year":"2012","unstructured":"N Singh, MP Frushicheva, A Warshel, Validating the vitality strategy for fighting drug resistance. Proteins 80, 1110\u20131122 (2012).","journal-title":"Proteins"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1002\/prot.22687","article-title":"Absolute binding free energy calculations: On the accuracy of computational scoring of protein-ligand interactions","volume":"78","author":"Singh N","year":"2010","unstructured":"N Singh, A Warshel, Absolute binding free energy calculations: On the accuracy of computational scoring of protein-ligand interactions. Proteins 78, 1705\u20131723 (2010).","journal-title":"Proteins"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1002\/prot.20021","article-title":"Probing flexibility and \u201cinduced-fit\u201d phenomena in aldose reductase by comparative crystal structure analysis and molecular dynamics simulations","volume":"56","author":"Sotriffer CA","year":"2004","unstructured":"CA Sotriffer, O Kr\u00e4mer, G Klebe, Probing flexibility and \u201cinduced-fit\u201d phenomena in aldose reductase by comparative crystal structure analysis and molecular dynamics simulations. Proteins 56, 52\u201366 (2004).","journal-title":"Proteins"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/cbic.200300644","article-title":"Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design","volume":"4","author":"Brenk R","year":"2003","unstructured":"R Brenk, MT Stubbs, A Heine, K Reuter, G Klebe, Flexible adaptations in the structure of the tRNA-modifying enzyme tRNA-guanine transglycosylase and their implications for substrate selectivity, reaction mechanism and structure-based drug design. ChemBioChem 4, 1066\u20131077 (2003).","journal-title":"ChemBioChem"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nsb0194-55","article-title":"Analogous inhibitors of elastase do not always bind analogously","volume":"1","author":"Mattos C","year":"1994","unstructured":"C Mattos, B Rasmussen, X Ding, GA Petsko, D Ringe, Analogous inhibitors of elastase do not always bind analogously. Nat Struct Biol 1, 55\u201358 (1994).","journal-title":"Nat Struct Biol"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"8564","DOI":"10.1021\/bi00027a006","article-title":"Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme","volume":"34","author":"Morton A","year":"1995","unstructured":"A Morton, WA Baase, BW Matthews, Energetic origins of specificity of ligand binding in an interior nonpolar cavity of T4 lysozyme. Biochemistry 34, 8564\u20138575 (1995).","journal-title":"Biochemistry"},{"key":"e_1_3_4_21_2","doi-asserted-by":"crossref","first-page":"8576","DOI":"10.1021\/bi00027a007","article-title":"Specificity of ligand binding in a buried nonpolar cavity of T4 lysozyme: Linkage of dynamics and structural plasticity","volume":"34","author":"Morton A","year":"1995","unstructured":"A Morton, BW Matthews, Specificity of ligand binding in a buried nonpolar cavity of T4 lysozyme: Linkage of dynamics and structural plasticity. Biochemistry 34, 8576\u20138588 (1995).","journal-title":"Biochemistry"},{"key":"e_1_3_4_22_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.jmb.2009.09.049","article-title":"Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site","volume":"394","author":"Boyce SE","year":"2009","unstructured":"SE Boyce, , Predicting ligand binding affinity with alchemical free energy methods in a polar model binding site. 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J Chem Theory Comput 3, 1231\u20131235 (2007).","journal-title":"J Chem Theory Comput"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1007\/s10822-013-9689-8","article-title":"Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics","volume":"27","author":"Wang K","year":"2013","unstructured":"K Wang, JD Chodera, Y Yang, MR Shirts, Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics. 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J Chem Theory Comput 10, 1314\u20131325 (2014).","journal-title":"J Chem Theory Comput"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1021\/ct500201y","article-title":"Sampling of organic solutes in aqueous and heterogeneous environments using oscillating excess chemical potentials in grand canonical-like Monte Carlo-molecular dynamics simulations","volume":"10","author":"Lakkaraju SK","year":"2014","unstructured":"SK Lakkaraju, EP Raman, W Yu, Jr AD MacKerell, Sampling of organic solutes in aqueous and heterogeneous environments using oscillating excess chemical potentials in grand canonical-like Monte Carlo-molecular dynamics simulations. J Chem Theory Comput 10, 2281\u20132290 (2014).","journal-title":"J Chem Theory Comput"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature10349","article-title":"Solution structure of a minor and transiently formed state of a T4 lysozyme mutant","volume":"477","author":"Bouvignies G","year":"2011","unstructured":"G Bouvignies, , Solution structure of a minor and transiently formed state of a T4 lysozyme mutant. Nature 477, 111\u2013114 (2011).","journal-title":"Nature"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","article-title":"PHENIX: A comprehensive Python-based system for macromolecular structure solution","volume":"66","author":"Adams PD","year":"2010","unstructured":"PD Adams, , PHENIX: A comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D Biol Crystallogr 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nchem.1954","article-title":"Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery","volume":"6","author":"Fischer M","year":"2014","unstructured":"M Fischer, RG Coleman, JS Fraser, BK Shoichet, Incorporation of protein flexibility and conformational energy penalties in docking screens to improve ligand discovery. Nat Chem 6, 575\u2013583 (2014).","journal-title":"Nat Chem"},{"key":"e_1_3_4_32_2","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1063\/1.555833","article-title":"Octanol-water partition coefficients of simple organic compounds","volume":"18","author":"Sangster J","year":"1989","unstructured":"J Sangster, Octanol-water partition coefficients of simple organic compounds. J Phys Chem Ref Data 18, 1111\u20131227 (1989).","journal-title":"J Phys Chem Ref Data"},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1021\/ci970437z","article-title":"On the properties of bit string-based measures of chemical similarity","volume":"38","author":"Flower DR","year":"1998","unstructured":"DR Flower, On the properties of bit string-based measures of chemical similarity. J Chem Inf Comput Sci 38, 379\u2013386 (1998).","journal-title":"J Chem Inf Comput Sci"},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1021\/ci900108d","article-title":"Development of a compound class-directed similarity coefficient that accounts for molecular complexity effects in fingerprint searching","volume":"49","author":"Wang Y","year":"2009","unstructured":"Y Wang, J Bajorath, Development of a compound class-directed similarity coefficient that accounts for molecular complexity effects in fingerprint searching. J Chem Inf Model 49, 1369\u20131376 (2009).","journal-title":"J Chem Inf Model"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jmb.2012.01.054","article-title":"Impact of ligand and protein desolvation on ligand binding to the S1 pocket of thrombin","volume":"418","author":"Biela A","year":"2012","unstructured":"A Biela, , Impact of ligand and protein desolvation on ligand binding to the S1 pocket of thrombin. J Mol Biol 418, 350\u2013366 (2012).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"17448","DOI":"10.1073\/pnas.1208337109","article-title":"Fragment-guided design of subnanomolar \u03b2-lactamase inhibitors active in vivo","volume":"109","author":"Eidam O","year":"2012","unstructured":"O Eidam, , Fragment-guided design of subnanomolar \u03b2-lactamase inhibitors active in vivo. Proc Natl Acad Sci USA 109, 17448\u201317453 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"14017","DOI":"10.1021\/ja2045293","article-title":"Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the \u201chydrophobic wall\u201d of carbonic anhydrase","volume":"133","author":"Mecinovi\u0107 J","year":"2011","unstructured":"J Mecinovi\u0107, , Fluoroalkyl and alkyl chains have similar hydrophobicities in binding to the \u201chydrophobic wall\u201d of carbonic anhydrase. J Am Chem Soc 133, 14017\u201314026 (2011).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.jmb.2003.11.041","article-title":"Understanding protein-ligand interactions: The price of protein flexibility","volume":"335","author":"Rauh D","year":"2004","unstructured":"D Rauh, G Klebe, MT Stubbs, Understanding protein-ligand interactions: The price of protein flexibility. J Mol Biol 335, 1325\u20131341 (2004).","journal-title":"J Mol Biol"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/cmdc.201400013","article-title":"Methyl, ethyl, propyl, butyl: Futile but not for water, as the correlation of structure and thermodynamic signature shows in a congeneric series of thermolysin inhibitors","volume":"9","author":"Krimmer SG","year":"2014","unstructured":"SG Krimmer, M Betz, A Heine, G Klebe, Methyl, ethyl, propyl, butyl: Futile but not for water, as the correlation of structure and thermodynamic signature shows in a congeneric series of thermolysin inhibitors. ChemMedChem 9, 833\u2013846 (2014).","journal-title":"ChemMedChem"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1021\/bi400413c","article-title":"Rational optimization of drug-target residence time: Insights from inhibitor binding to the Staphylococcus aureus FabI enzyme-product complex","volume":"52","author":"Chang A","year":"2013","unstructured":"A Chang, , Rational optimization of drug-target residence time: Insights from inhibitor binding to the Staphylococcus aureus FabI enzyme-product complex. Biochemistry 52, 4217\u20134228 (2013).","journal-title":"Biochemistry"},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1002\/cbic.201200433","article-title":"Synthesis and structural characterisation of selective non-carbohydrate-based inhibitors of bacterial sialidases","volume":"13","author":"Brear P","year":"2012","unstructured":"P Brear, J Telford, GL Taylor, NJ Westwood, Synthesis and structural characterisation of selective non-carbohydrate-based inhibitors of bacterial sialidases. ChemBioChem 13, 2374\u20132383 (2012).","journal-title":"ChemBioChem"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1038\/nchembio.1214","article-title":"Ligand-binding dynamics rewire cellular signaling via estrogen receptor-\u03b1","volume":"9","author":"Srinivasan S","year":"2013","unstructured":"S Srinivasan, , Ligand-binding dynamics rewire cellular signaling via estrogen receptor-\u03b1. Nat Chem Biol 9, 326\u2013332 (2013).","journal-title":"Nat Chem Biol"},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1110\/ps.03259908","article-title":"Allostery and cooperativity revisited","volume":"17","author":"Cui Q","year":"2008","unstructured":"Q Cui, M Karplus, Allostery and cooperativity revisited. Protein Sci 17, 1295\u20131307 (2008).","journal-title":"Protein Sci"},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/prot.20232","article-title":"Is allostery an intrinsic property of all dynamic proteins?","volume":"57","author":"Gunasekaran K","year":"2004","unstructured":"K Gunasekaran, B Ma, R Nussinov, Is allostery an intrinsic property of all dynamic proteins? Proteins 57, 433\u2013443 (2004).","journal-title":"Proteins"},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-biophys-042910-155245","article-title":"Biomolecular simulation: A computational microscope for molecular biology","volume":"41","author":"Dror RO","year":"2012","unstructured":"RO Dror, RM Dirks, JP Grossman, H Xu, DE Shaw, Biomolecular simulation: A computational microscope for molecular biology. Annu Rev Biophys 41, 429\u2013452 (2012).","journal-title":"Annu Rev Biophys"},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"18413","DOI":"10.1021\/ja207470h","article-title":"Markov state model reveals folding and functional dynamics in ultra-long MD trajectories","volume":"133","author":"Lane TJ","year":"2011","unstructured":"TJ Lane, GR Bowman, K Beauchamp, VA Voelz, VS Pande, Markov state model reveals folding and functional dynamics in ultra-long MD trajectories. J Am Chem Soc 133, 18413\u201318419 (2011).","journal-title":"J Am Chem Soc"},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.sbi.2012.11.002","article-title":"To milliseconds and beyond: Challenges in the simulation of protein folding","volume":"23","author":"Lane TJ","year":"2013","unstructured":"TJ Lane, D Shukla, KA Beauchamp, VS Pande, To milliseconds and beyond: Challenges in the simulation of protein folding. 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