{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:46:18Z","timestamp":1772171178912,"version":"3.50.1"},"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T00:00:00Z","timestamp":1303948800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1002037","type":"journal-article","created":{"date-parts":[[2011,4,28]],"date-time":"2011-04-28T17:03:42Z","timestamp":1304010222000},"page":"e1002037","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":146,"title":["Drug Discovery Using Chemical Systems Biology: Weak Inhibition of Multiple Kinases May Contribute to the Anti-Cancer Effect of Nelfinavir"],"prefix":"10.1371","volume":"7","author":[{"given":"Li","family":"Xie","sequence":"first","affiliation":[]},{"given":"Thomas","family":"Evangelidis","sequence":"additional","affiliation":[]},{"given":"Lei","family":"Xie","sequence":"additional","affiliation":[]},{"given":"Philip E.","family":"Bourne","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2011,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nchembio.117","article-title":"Targeted polypharmacology: discovery of dual inhibitors of tyrosine and phosphoinositide kinases.","volume":"4","author":"B Apsel","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nchembio817","article-title":"Systems biology and combination therapy in the quest for clinical efficacy.","volume":"2","author":"JB Fitzgerald","year":"2006","journal-title":"Nat Chem Biol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/nbt1007-1110","article-title":"Network pharmacology.","volume":"25","author":"AL Hopkins","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.drudis.2006.11.008","article-title":"Multi-target therapeutics: when the whole is greater than the sum of the parts.","volume":"12","author":"GR Zimmermann","year":"2007","journal-title":"Drug Discov Today"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrd2195","article-title":"A robustness-based approach to systems-oriented drug design.","volume":"6","author":"H Kitano","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nchembio.118","article-title":"Network pharmacology: the next paradigm in drug discovery.","volume":"4","author":"AL Hopkins","year":"2008","journal-title":"Nat Chem Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrd2683","article-title":"Mechanisms of drug combinations: interaction and network perspectives.","volume":"8","author":"J Jia","year":"2009","journal-title":"Nat Rev Drug Discov"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"422","DOI":"10.2174\/092986708783503212","article-title":"From single- to multi-target drugs in cancer therapy: when aspecificity becomes an advantage.","volume":"15","author":"A Petrelli","year":"2008","journal-title":"Curr Med Chem"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.tips.2005.02.007","article-title":"The efficiency of multi-target drugs: the network approach might help drug design.","volume":"26","author":"P Csermely","year":"2005","journal-title":"Trends Pharmacol Sci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.sbi.2006.01.013","article-title":"Can we rationally design promiscuous drugs?","volume":"16","author":"AL Hopkins","year":"2006","journal-title":"Curr Opin Struct Biol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/nrc2787","article-title":"Targeting the cancer kinome through polypharmacology.","volume":"10","author":"ZA Knight","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e1000423","DOI":"10.1371\/journal.pcbi.1000423","article-title":"Drug discovery using chemical systems biology: repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis.","volume":"5","author":"SL Kinnings","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e1000387","DOI":"10.1371\/journal.pcbi.1000387","article-title":"Drug discovery using chemical systems biology: identification of the protein-ligand binding network to explain the side effects of CETP inhibitors.","volume":"5","author":"L Xie","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"e1000648","DOI":"10.1371\/journal.pcbi.1000648","article-title":"A multidimensional strategy to detect polypharmacological targets in the absence of structural and sequence homology.","volume":"6","author":"JD Durrant","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"051909","DOI":"10.1103\/PhysRevE.71.051909","article-title":"Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example.","volume":"71","author":"V Agoston","year":"2005","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1126\/science.1162327","article-title":"Diversity and complexity in DNA recognition by transcription factors.","volume":"324","author":"G Badis","year":"2009","journal-title":"Science"},{"key":"ref17","first-page":"re9","article-title":"Cracking the phosphatase code: docking interactions determine substrate specificity.","volume":"2","author":"J Roy","year":"2009","journal-title":"Sci Signal"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev.biophys.36.040306.132550","article-title":"Calculation of protein-ligand binding affinities.","volume":"36","author":"MK Gilson","year":"2007","journal-title":"Ann Rev Biophys Biomol Struct"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.str.2009.02.010","article-title":"Binding of small-molecule ligands to proteins: \u201cwhat you see\u201d is not always \u201cwhat you get\u201d.","volume":"17","author":"DL Mobley","year":"2009","journal-title":"Structure"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jmb.2007.06.002","article-title":"Predicting absolute ligand binding free energies to a simple model site.","volume":"371","author":"DL Mobley","year":"2007","journal-title":"J Mol Biol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.1186\/1471-2105-8-S4-S9","article-title":"A robust and efficient algorithm for the shape description of protein structures and its application in predicting ligand binding sites.","volume":"8","author":"L Xie","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1073\/pnas.0704422105","article-title":"Detecting evolutionary relationships across existing fold space, using sequence order-independent profile\u2013profile alignments.","volume":"105","author":"L Xie","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"i305","DOI":"10.1093\/bioinformatics\/btp220","article-title":"A unified statistical model to support local sequence order independent similarity searching for ligand binding sites and its application to genome-based drug discovery.","volume":"25","author":"L Xie","year":"2009","journal-title":"Bioinformatics"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1097\/01.cad.0000224448.08706.76","article-title":"Nelfinavir induces liposarcoma apoptosis and cell cycle arrest by upregulating sterol regulatory element binding protein-1.","volume":"17","author":"WA Chow","year":"2006","journal-title":"Anticancer Drugs"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.1158\/1078-0432.CCR-07-0161","article-title":"Nelfinavir, a lead HIV protease inhibitor, is a broad-spectrum, anticancer agent that induces endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo.","volume":"13","author":"J Gills","year":"2007","journal-title":"Clin Cancer Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S1470-2045(08)70334-6","article-title":"Anti-HIV drugs for cancer therapeutics: back to the future?","volume":"10","author":"WA Chow","year":"2009","journal-title":"Lancet Oncol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"628","DOI":"10.4161\/cbt.7.5.5728","article-title":"Validation and Toxicity of PI3K\/Akt Pathway Inhibition by HIV Protease Inhibitors in Humans.","volume":"7","author":"JP Plastaras","year":"2008","journal-title":"Cancer Biol Ther"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nature05933","article-title":"(448) A transforming mutation in the pleckstrin homology domain of AKT1 in cancer.","volume":"448","author":"JD Carpten","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.cellsig.2006.05.019","article-title":"Role of PI3K and AKT specific isoforms in ovarian cancer cell migration, invasion and proliferation through the p70S6K1 pathway.","volume":"18","author":"Q Meng","year":"2006","journal-title":"Cell Signal"},{"key":"ref30","first-page":"7738","article-title":"Akt1 governs breast cancer progression in vivo.","volume":"104","author":"X Ju","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.febslet.2004.03.116","article-title":"Selectivity and promiscuity in the interaction network mediated by protein recognition modules.","volume":"567","author":"L Castagnoli","year":"2004","journal-title":"FEBS Lett"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"8256","DOI":"10.1158\/0008-5472.CAN-05-1220","article-title":"HIV protease inhibitors block Akt signaling and radiosensitize tumor cells both in vitro and in vivo.","volume":"65","author":"AK Gupta","year":"2005","journal-title":"Cancer Res"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10822-007-9114-2","article-title":"Surflex-Dock 2.1: robust performance from ligand energetic modeling, ring flexibility, and knowledge-based search.","volume":"21","author":"AN Jain","year":"2007","journal-title":"J Comput Aided Mol Des"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jmgm.2006.06.002","article-title":"eHiTS: a new fast, exhaustive flexible ligand docking system.","volume":"26","author":"Z Zsoldos","year":"2007","journal-title":"J Mol Graph Model"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.1126\/science.1075762","article-title":"The protein kinase complement of the human genome.","volume":"298","author":"G Manning","year":"2002","journal-title":"Science"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/jcc.21372","article-title":"Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA.","volume":"31","author":"G Rastelli","year":"2009","journal-title":"J Comput Chem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/j.1747-0285.2010.01028.x","article-title":"Molecular dynamics simulations of 2-amino-6-arylsulphonylbenzonitriles analogues as HIV inhibitors: interaction modes and binding free energies.","volume":"76","author":"R Hu","year":"2010","journal-title":"Chem Biol Drug Des"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"8435","DOI":"10.1021\/bi900729a","article-title":"Quantitative prediction of fold resistance for inhibitors of EGFR.","volume":"48","author":"TE Balius","year":"2009","journal-title":"Biochemistry"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1021\/jm701021b","article-title":"Kinase-likeness and kinase-privileged fragments: toward virtual polypharmacology.","volume":"51","author":"AM Aronov","year":"2008","journal-title":"J Med Chem"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nchembio866","article-title":"Structure-guided development of affinity probes for tyrosine kinases using chemical genetics.","volume":"3","author":"JA Blair","year":"2007","journal-title":"Nat Chem Biol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1097\/COH.0b013e328313915d","article-title":"Repositioning HIV protease inhibitors as cancer therapeutics.","volume":"3","author":"WB Bernstein","year":"2008","journal-title":"Curr Opin HIV AIDS"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1186\/bcr2602","article-title":"Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells.","volume":"12","author":"A Bruning","year":"2010","journal-title":"Breast Cancer Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"e1000662","DOI":"10.1371\/journal.pcbi.1000662","article-title":"Network-based elucidation of human disease similarities reveals common functional modules enriched for pluripotent drug targets.","volume":"6","author":"S Suthram","year":"2010","journal-title":"PLoS Comput Biol"},{"key":"ref44","first-page":"1","article-title":"RTK\/Ras\/MAPK signaling.","author":"MV Sundaram","year":"2006"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/1471-213X-9-53","article-title":"Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye.","volume":"9","author":"Y Wu","year":"2009","journal-title":"BMC Dev Biol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1242\/jcs.009530","article-title":"Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis.","volume":"121","author":"S Maddika","year":"2008","journal-title":"J Cell Sci"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nrd3024","article-title":"Teaching old receptors new tricks: biasing seven-transmembrane receptors.","volume":"9","author":"S Rajagopal","journal-title":"Nat Rev Drug Discov"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nbt1284","article-title":"Relating protein pharmacology by ligand chemistry.","volume":"25","author":"MJ Keiser","year":"2007","journal-title":"Nat Biotechnol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nature08506","article-title":"Predicting new molecular targets for known drugs.","volume":"462","author":"MJ Keiser","year":"2009","journal-title":"Nature"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/nrd2195","article-title":"A robustness-based approach to systems-oriented drug design.","volume":"6","author":"H Kitano","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1126\/science.1155174","article-title":"Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.","volume":"320","author":"T Walsh","year":"2008","journal-title":"Science"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1126\/science.1164382","article-title":"An Integrated Genomic Analysis of Human Glioblastoma Multiforme.","volume":"321","year":"2008","journal-title":"Science"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1126\/science.1164368","article-title":"Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses.","volume":"321","year":"2008","journal-title":"Science"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nbt0605-639","article-title":"Multi-kinase inhibitors create buzz at ASCO.","volume":"23","author":"MA Branca","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nbt1068","article-title":"A small molecule-kinase interaction map for clinical kinase inhibitors.","volume":"23","author":"MA Fabian","year":"2005","journal-title":"Nat Biotechnol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"35ra41","DOI":"10.1126\/scitranslmed.3000758","article-title":"Gatekeeper mutations mediate resistance to BRAF-targeted therapies.","volume":"2","author":"S Whittaker","year":"2010","journal-title":"Sci Transl Med"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.biosystems.2004.10.002","article-title":"A mathematical model of combination therapy using the EGFR signaling network.","volume":"80","author":"RP Araujo","year":"2005","journal-title":"Biosystems"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1038\/nrd2381","article-title":"Proteins, drug targets and the mechanisms they control: the simple truth about complex networks.","volume":"6","author":"RP Araujo","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/msb.2008.53","article-title":"Models from experiments: combinatorial drug perturbations of cancer cells.","volume":"4","author":"S Nelander","year":"2008","journal-title":"Mol Syst Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/msb.2008.60","article-title":"Finding multiple target optimal intervention in disease-related molecular network.","volume":"4","author":"K Yang","year":"2008","journal-title":"Mol Syst Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"6704","DOI":"10.1158\/0008-5472.CAN-10-0460","article-title":"Identification of optimal drug combinations targeting cellular networks: integrating phospho-proteomics and computational network analysis.","volume":"70","author":"S Iadevaia","year":"2010","journal-title":"Cancer Res"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrd1467","article-title":"Fragment-based lead discovery.","volume":"3","author":"DC Rees","year":"2004","journal-title":"Nat Rev Drug Discov"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.tips.2009.07.004","article-title":"Conciliating binding efficiency and polypharmacology.","volume":"30","author":"J Mestres","year":"2009","journal-title":"Trends Pharmacol Sci"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.cbpa.2010.06.176","article-title":"Drug-target residence time: critical information for lead optimization.","volume":"14","author":"H Lu","year":"2010","journal-title":"Curr Opin Chem Biol"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/nrd2082","article-title":"Drug-target residence time and its implications for lead optimization.","volume":"5","author":"RA Copeland","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s11095-010-0065-2","article-title":"In-silico approaches to multi-target drug discovery: computer aided multi-target drug design, multi-target virtual screening.","volume":"27","author":"XH Ma","year":"2010","journal-title":"Pharm Res"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"e1000938","DOI":"10.1371\/journal.pcbi.1000938","article-title":"Drug off-Target effects predicted using structural analysis in the context of a metabolic network model.","volume":"6","author":"RL Chang","year":"2010","journal-title":"PLoS Comp Biol"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1093\/bib\/bbl043","article-title":"Computational methodologies for modelling, analysis and simulation of signalling networks.","volume":"7","author":"D Gilbert","year":"2006","journal-title":"Brief Bioinform"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models.","volume":"33","author":"PA Kollman","year":"2000","journal-title":"Acc Chem Res"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1529\/biophysj.105.071589","article-title":"Calculation of absolute protein-ligand binding affinity using path and endpoint approaches.","volume":"90","author":"MS Lee","year":"2006","journal-title":"Biophys J"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"e1000546","DOI":"10.1371\/journal.pcbi.1000546","article-title":"Investigation of the Interaction between the Large and Small Subunits of Potato ADP-Glucose Pyrophosphorylase.","volume":"5","author":"I Baris","year":"2009","journal-title":"PLoS Comput Biol"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s10822-009-9298-8","article-title":"Studies of chirality effect of 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine on p38alpha by molecular dynamics simulations and free energy calculations.","volume":"23","author":"Q Chen","year":"2009","journal-title":"J Comput Aided Mol Des"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jmgm.2009.06.002","article-title":"Molecular modeling of human cytochrome P450 2W1 and its interactions with substrates.","volume":"28","author":"WH Li","year":"2009","journal-title":"J Mol Graph Model"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"13709","DOI":"10.1021\/ja9039373","article-title":"Importance of Ligand Reorganization Free Energy in Protein-Ligand Binding-Affinity Prediction.","volume":"131","author":"CY Yang","year":"2009","journal-title":"J Am Chem Soc"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD.","volume":"26","author":"JC Phillips","year":"2005","journal-title":"J Comput Chem"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.","volume":"31","author":"O Trott","year":"2009","journal-title":"J Comput Chem"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water.","volume":"79","author":"WL Jorgensen","year":"1983","journal-title":"J Chem Phys"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"10089","DOI":"10.1063\/1.464397","article-title":"Particle Mesh Ewald - an N.Log(N) Method for Ewald Sums in Large Systems.","volume":"98","author":"T Darden","year":"1993","journal-title":"J Chem Phys"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical Integration of the Cartesian Equations of Motion of a System with Constraints: Molecular Dynamics of n-Alkanes.","volume":"23","author":"J-PCG Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1063\/1.467468","article-title":"Constant-Pressure Molecular-Dynamics Algorithms.","volume":"101","author":"GJ Martyna","year":"1994","journal-title":"J Chem Phys"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"4613","DOI":"10.1063\/1.470648","article-title":"Constant-Pressure Molecular-Dynamics Simulation - the Langevin Piston Method.","volume":"103","author":"SE Feller","year":"1995","journal-title":"J Chem Phys"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"4997","DOI":"10.1103\/PhysRevB.39.4997","article-title":"Conjugate-Gradient Minimization of the Energy Functional - a New Method for Electronic-Structure Calculation.","volume":"39","author":"I Stich","year":"1989","journal-title":"Phys Rev B"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0065-3233(03)66002-X","article-title":"Force fields for protein simulations.","volume":"66","author":"JW Ponder","year":"2003","journal-title":"Adv Protein Chem"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs.","volume":"26","author":"DA Case","year":"2005","journal-title":"J Comput Chem"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1021\/jp9521621","article-title":"A comprehensive analytical treatment of continuum electrostatics.","volume":"100","author":"M Schaefer","year":"1996","journal-title":"J Phys Chem"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"9571","DOI":"10.1021\/jp982007x","article-title":"Solvation free energy of biomacromolecules: Parameters for a modified generalized born model consistent with the AMBER force field.","volume":"102","author":"B Jayaram","year":"1998","journal-title":"J Phy Chem B"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1146\/annurev.physchem.51.1.129","article-title":"Generalized born models of macromolecular solvation effects.","volume":"51","author":"D Bashford","year":"2000","journal-title":"Ann Rev Phys Chem"},{"key":"ref88","first-page":"C47","article-title":"Generalized born models of macromolecular solvation effects.","volume":"223","author":"DA Case","year":"2002","journal-title":"Abst Papers Am Chem Soc"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1021\/jp994072s","article-title":"Modification of the generalized Born model suitable for macromolecules.","volume":"104","author":"A Onufriev","year":"2000","journal-title":"J Phys Chem B"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/jcc.10378","article-title":"Performance comparison of generalized born and Poisson methods in the calculation of electrostatic solvation energies for protein structures.","volume":"25","author":"M Feig","year":"2004","journal-title":"J Comput Chem"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/prot.20033","article-title":"Exploring protein native states and large-scale conformational changes with a modified generalized born model.","volume":"55","author":"A Onufriev","year":"2004","journal-title":"Proteins"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1021\/j100058a043","article-title":"Accurate Calculation of Hydration Free-Energies Using Macroscopic Solvent Models.","volume":"98","author":"D Sitkoff","year":"1994","journal-title":"J Phys Chem"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/(SICI)1096-987X(19990130)20:2<217::AID-JCC4>3.0.CO;2-A","article-title":"Approximate atomic surfaces from linear combinations of pairwise overlaps (LCPO).","volume":"20","author":"J Weiser","year":"1999","journal-title":"J Comput Chem"},{"key":"ref94","doi-asserted-by":"crossref","first-page":"9401","DOI":"10.1021\/ja981844+","article-title":"Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate - DNA helices.","volume":"120","author":"J Srinivasan","year":"1998","journal-title":"J Am Chem Soc"},{"key":"ref95","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/(SICI)1097-0134(20000601)39:4<309::AID-PROT40>3.0.CO;2-S","article-title":"Use of MM-PB\/SA in estimating the free energies of proteins: Application to native, intermediates, and unfolded villin headpiece.","volume":"39","author":"MR Lee","year":"2000","journal-title":"Proteins"},{"key":"ref96","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.1073\/pnas.80.21.6571","article-title":"Harmonic Dynamics of Proteins - Normal-Modes and Fluctuations in Bovine Pancreatic Trypsin-Inhibitor.","volume":"80","author":"B Brooks","year":"1983","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T08:02:39Z","timestamp":1712390559000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1002037"}},"subtitle":[],"editor":[{"given":"Ruth","family":"Nussinov","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2011,4,28]]},"references-count":96,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2011,4,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1002037","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.12266956.14199057","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,4,28]]}}}