{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T01:40:23Z","timestamp":1782178823778,"version":"3.54.5"},"reference-count":89,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"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.1003874","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T17:58:52Z","timestamp":1412877532000},"page":"e1003874","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Predicting the Functions and Specificity of Triterpenoid Synthases: A Mechanism-Based Multi-intermediate Docking Approach"],"prefix":"10.1371","volume":"10","author":[{"given":"Bo-Xue","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H.","family":"Wallrapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma L.","family":"Holiday","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng-Yeong","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia C.","family":"Babbitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Dale","family":"Poulter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/180470a0","article-title":"The Chemistry of Terpenoid Compounds","volume":"180","author":"AJ Birch","year":"1957","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1126\/science.277.5333.1788","article-title":"Biochemistry - Creating isoprenoid diversity","volume":"277","author":"JC Sacchettini","year":"1997","journal-title":"Science"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.cbpa.2007.12.008","article-title":"Unearthing the roots of the terpenome","volume":"12","author":"DW Christianson","year":"2008","journal-title":"Curr Opin Chem Biol"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"4126","DOI":"10.1073\/pnas.95.8.4126","article-title":"Plant terpenoid synthases: molecular biology and phylogenetic analysis","volume":"95","author":"J Bohlmann","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1021\/cr050286w","article-title":"Structural biology and chemistry of the terpenoid cyclases","volume":"106","author":"DW Christianson","year":"2006","journal-title":"Chem Rev"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1039\/c2np20059g","article-title":"Terpenoid synthase structures: a so far incomplete view of complex catalysis","volume":"29","author":"Y Gao","year":"2012","journal-title":"Nat Prod Rep"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1002\/anie.201103110","article-title":"Terpene biosynthesis: modularity rules","volume":"51","author":"E Oldfield","year":"2012","journal-title":"Angew Chem Int Ed Engl"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1073\/pnas.0700915104","article-title":"Structure of limonene synthase, a simple model for terpenoid cyclase catalysis","volume":"104","author":"DC Hyatt","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1006\/jmbi.1998.2470","article-title":"The structure of the membrane protein squalene-hopene cyclase at 2.0 A resolution","volume":"286","author":"KU Wendt","year":"1999","journal-title":"J Mol Biol"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1126\/science.277.5333.1811","article-title":"Structure and function of a squalene cyclase","volume":"277","author":"KU Wendt","year":"1997","journal-title":"Science"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1039\/C1NP00060H","article-title":"Sesquiterpene synthases: passive catalysts or active players?","volume":"29","author":"DJ Miller","year":"2012","journal-title":"Nat Prod Rep"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1002\/1521-3773(20000818)39:16<2812::AID-ANIE2812>3.0.CO;2-#","article-title":"Enzyme Mechanisms for Polycyclic Triterpene Formation","volume":"39","author":"KU Wendt","year":"2000","journal-title":"Angew Chem Int Ed Engl"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"6840","DOI":"10.1074\/jbc.M111.337592","article-title":"Insights into diterpene cyclization from structure of bifunctional abietadiene synthase from Abies grandis","volume":"287","author":"K Zhou","year":"2012","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"11213","DOI":"10.1021\/ja073133u","article-title":"An oxidosqualene cyclase makes numerous products by diverse mechanisms: a challenge to prevailing concepts of triterpene biosynthesis","volume":"129","author":"S Lodeiro","year":"2007","journal-title":"J Am Chem Soc"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature02993","article-title":"Insight into steroid scaffold formation from the structure of human oxidosqualene cyclase","volume":"432","author":"R Thoma","year":"2004","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"6414","DOI":"10.1021\/ja058782p","article-title":"Site-saturated mutagenesis of histidine 234 of Saccharomyces cerevisiae oxidosqualene-lanosterol cyclase demonstrates dual functions in cyclization and rearrangement reactions","volume":"128","author":"TK Wu","year":"2006","journal-title":"J Am Chem Soc"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1126\/science.277.5333.1820","article-title":"Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology","volume":"277","author":"CA Lesburg","year":"1997","journal-title":"Science"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1126\/science.277.5333.1815","article-title":"Structural basis for cyclic terpene biosynthesis by tobacco 5-epi-aristolochene synthase","volume":"277","author":"CM Starks","year":"1997","journal-title":"Science"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"15375","DOI":"10.1073\/pnas.232591099","article-title":"Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase","volume":"99","author":"DA Whittington","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"12719","DOI":"10.1021\/bi0510476","article-title":"Role of arginine-304 in the diphosphate-triggered active site closure mechanism of trichodiene synthase","volume":"44","author":"LS Vedula","year":"2005","journal-title":"Biochemistry"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1105\/tpc.106.047779","article-title":"Rational conversion of substrate and product specificity in a Salvia monoterpene synthase: structural insights into the evolution of terpene synthase function","volume":"19","author":"SC Kampranis","year":"2007","journal-title":"Plant Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"15431","DOI":"10.1074\/jbc.M800659200","article-title":"X-ray crystallographic studies of substrate binding to aristolochene synthase suggest a metal ion binding sequence for catalysis","volume":"283","author":"EY Shishova","year":"2008","journal-title":"J Biol Chem"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"6175","DOI":"10.1021\/bi900483b","article-title":"Crystal structure of (+)-delta-cadinene synthase from Gossypium arboreum and evolutionary divergence of metal binding motifs for catalysis","volume":"48","author":"HA Gennadios","year":"2009","journal-title":"Biochemistry"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1021\/bi902088z","article-title":"Structure of epi-isozizaene synthase from Streptomyces coelicolor A3(2), a platform for new terpenoid cyclization templates","volume":"49","author":"JA Aaron","year":"2010","journal-title":"Biochemistry"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/cb900295g","article-title":"Structural elucidation of cisoid and transoid cyclization pathways of a sesquiterpene synthase using 2-fluorofarnesyl diphosphates","volume":"5","author":"JP Noel","year":"2010","journal-title":"ACS Chem Biol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nature09628","article-title":"Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis","volume":"469","author":"M Koksal","year":"2011","journal-title":"Nature"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1016\/j.str.2011.09.013","article-title":"Structure of a three-domain sesquiterpene synthase: a prospective target for advanced biofuels production","volume":"19","author":"RP McAndrew","year":"2011","journal-title":"Structure"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1021\/bi400691v","article-title":"Mechanistic insights from the binding of substrate and carbocation intermediate analogues to aristolochene synthase","volume":"52","author":"M Chen","year":"2013","journal-title":"Biochemistry"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/cbic.201300708","article-title":"Hedycaryol synthase in complex with nerolidol reveals terpene cyclase mechanism","volume":"15","author":"P Baer","year":"2014","journal-title":"Chembiochem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1021\/bi401643u","article-title":"Reprogramming the chemodiversity of terpenoid cyclization by remolding the active site contour of epi-isozizaene synthase","volume":"53","author":"R Li","year":"2014","journal-title":"Biochemistry"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1039\/b917107j","article-title":"The carbocation continuum in terpene biosynthesis\u2013where are the secondary cations?","volume":"39","author":"DJ Tantillo","year":"2010","journal-title":"Chem Soc Rev"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1039\/c1np00006c","article-title":"Biosynthesis via carbocations: theoretical studies on terpene formation","volume":"28","author":"DJ Tantillo","year":"2011","journal-title":"Nat Prod Rep"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1039\/c3sc53293c","article-title":"Predicting pathways for terpene formation from first principles - routes to known and new sesquiterpenes","volume":"5","author":"M Isegawa","year":"2014","journal-title":"Chem Sci"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1021\/ja4106489","article-title":"Branching out from the bisabolyl cation. Unifying mechanistic pathways to barbatene, bazzanene, chamigrene, chamipinene, cumacrene, cuprenene, dunniene, isobazzanene, iso-gamma-bisabolene, isochamigrene, laurene, microbiotene, sesquithujene, sesquisabinene, thujopsene, trichodiene, and widdradiene sesquiterpenes","volume":"136","author":"YJ Hong","year":"2014","journal-title":"J Am Chem Soc"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nchem.1843","article-title":"Biosynthetic consequences of multiple sequential post-transition-state bifurcations","volume":"6","author":"YJ Hong","year":"2014","journal-title":"Nat Chem"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cbpa.2014.03.010","article-title":"Catalytic control in terpenoid cyclases: multiscale modeling of thermodynamic, kinetic, and dynamic effects","volume":"21C","author":"DT Major","year":"2014","journal-title":"Curr Opin Chem Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"6349","DOI":"10.1021\/ja910134x","article-title":"Challenges posed to bornyl diphosphate synthase: diverging reaction mechanisms in monoterpenes","volume":"132","author":"M Weitman","year":"2010","journal-title":"J Am Chem Soc"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"13857","DOI":"10.1021\/jp3091396","article-title":"Catalytic mechanism and product specificity of oxidosqualene-lanosterol cyclase: a QM\/MM study","volume":"116","author":"BX Tian","year":"2012","journal-title":"J Phys Chem B"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"12768","DOI":"10.1021\/ja0371799","article-title":"Balancing kinetic and thermodynamic control: the mechanism of carbocation cyclization by squalene cyclase","volume":"125","author":"R Rajamani","year":"2003","journal-title":"J Am Chem Soc"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"19454","DOI":"10.1021\/ja308295p","article-title":"Electrostatically guided dynamics\u2013the root of fidelity in a promiscuous terpene synthase?","volume":"134","author":"DT Major","year":"2012","journal-title":"J Am Chem Soc"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"11369","DOI":"10.1021\/ja3043245","article-title":"Effect of isotopically sensitive branching on product distribution for pentalenene synthase: support for a mechanism predicted by quantum chemistry","volume":"134","author":"L Zu","year":"2012","journal-title":"J Am Chem Soc"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1021\/ja309680b","article-title":"Assignment of pterin deaminase activity to an enzyme of unknown function guided by homology modeling and docking","volume":"135","author":"H Fan","year":"2013","journal-title":"J Am Chem Soc"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"9950","DOI":"10.1021\/bi201312u","article-title":"The Enzyme Function Initiative","volume":"50","author":"JA Gerlt","year":"2011","journal-title":"Biochemistry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nature05981","article-title":"Structure-based activity prediction for an enzyme of unknown function","volume":"448","author":"JC Hermann","year":"2007","journal-title":"Nature"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1016\/j.str.2008.08.015","article-title":"Discovery of a dipeptide epimerase enzymatic function guided by homology modeling and virtual screening","volume":"16","author":"C Kalyanaraman","year":"2008","journal-title":"Structure"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1021\/bi100445g","article-title":"Studying enzyme-substrate specificity in silico: a case study of the Escherichia coli glycolysis pathway","volume":"49","author":"C Kalyanaraman","year":"2010","journal-title":"Biochemistry"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"4122","DOI":"10.1073\/pnas.1112081109","article-title":"Homology models guide discovery of diverse enzyme specificities among dipeptide epimerases in the enolase superfamily","volume":"109","author":"T Lukk","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"11546","DOI":"10.1021\/bi901731c","article-title":"Computation-Facilitated Assignment of the Function in the Enolase Superfamily: A Regiochemically Distinct Galactarate Dehydratase from Oceanobacillus iheyensis","volume":"48","author":"JF Rakus","year":"2009","journal-title":"Biochemistry"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nchembio.2007.11","article-title":"Prediction and assignment of function for a divergent N-succinyl amino acid racemase","volume":"3","author":"L Song","year":"2007","journal-title":"Nat Chem Biol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"E1196","DOI":"10.1073\/pnas.1300632110","article-title":"Prediction of function for the polyprenyl transferase subgroup in the isoprenoid synthase superfamily","volume":"110","author":"FH Wallrapp","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1021\/bi400546j","article-title":"Predicting enzyme-substrate specificity with QM\/MM methods: a case study of the stereospecificity of (D)-glucarate dehydratase","volume":"52","author":"B Tian","year":"2013","journal-title":"Biochemistry"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nature12576","article-title":"Discovery of new enzymes and metabolic pathways by using structure and genome context","volume":"502","author":"S Zhao","year":"2013","journal-title":"Nature"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.tibs.2014.05.006","article-title":"Leveraging structure for enzyme function prediction: methods, opportunities, and challenges","volume":"39","author":"MP Jacobson","year":"2014","journal-title":"Trends Biochem Sci"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5362","DOI":"10.1021\/jo050147e","article-title":"Structure and reactivity of the dammarenyl cation: configurational transmission in triterpene synthesis","volume":"70","author":"Q Xiong","year":"2005","journal-title":"J Org Chem"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1021\/jp057109j","article-title":"Towards accurate ab initio QM\/MM calculations of free-energy profiles of enzymatic reactions","volume":"110","author":"E Rosta","year":"2006","journal-title":"J Phys Chem B"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1126\/science.1088172","article-title":"How enzymes work: Analysis by modern rate theory and computer simulations","volume":"303","author":"M Garcia-Viloca","year":"2004","journal-title":"Science"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1021\/cr050293k","article-title":"Mechanisms and free energies of enzymatic reactions","volume":"106","author":"J Gao","year":"2006","journal-title":"Chem Rev"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cbpa.2007.01.684","article-title":"QM\/MM studies of enzymes","volume":"11","author":"HM Senn","year":"2007","journal-title":"Curr Opin Chem Biol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1021\/bi400215w","article-title":"Combined quantum mechanics\/molecular mechanics (QM\/MM) methods in computational enzymology","volume":"52","author":"MW van der Kamp","year":"2013","journal-title":"Biochemistry"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nchembio.202","article-title":"Enzymatic transition states and dynamic motion in barrier crossing","volume":"5","author":"SD Schwartz","year":"2009","journal-title":"Nat Chem Biol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"e37674","DOI":"10.1371\/journal.pone.0037674","article-title":"QM\/MM MD and Free Energy Simulations of G9a-Like Protein (GLP) and Its Mutants: Understanding the Factors that Determine the Product Specificity","volume":"7","author":"YZ Chu","year":"2012","journal-title":"Plos One"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1002\/jcc.23403","article-title":"Convergence in the QM-only and QM\/MM modeling of enzymatic reactions: A case study for acetylene hydratase","volume":"34","author":"RZ Liao","year":"2013","journal-title":"J Comput Chem"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.phytochem.2003.11.014","article-title":"On the origins of triterpenoid skeletal diversity","volume":"65","author":"R Xu","year":"2004","journal-title":"Phytochemistry"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"6423","DOI":"10.1021\/cr200021m","article-title":"Biosynthesis of cholesterol and other sterols","volume":"111","author":"WD Nes","year":"2011","journal-title":"Chem Rev"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1039\/b108995c","article-title":"Squalene-hopene cyclase: catalytic mechanism and substrate recognition","author":"T Hoshino","year":"2002","journal-title":"Chem Commun (Camb)"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1002\/prot.24089","article-title":"The triterpene cyclase protein family: A systematic analysis","volume":"80","author":"S Racolta","year":"2012","journal-title":"Proteins-Structure Function and Bioinformatics"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"15882","DOI":"10.1021\/ja065860f","article-title":"Predicting substrates by docking high-energy intermediates to enzyme structures","volume":"128","author":"JC Hermann","year":"2006","journal-title":"J Am Chem Soc"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1021\/bi201838b","article-title":"Structure-based function discovery of an enzyme for the hydrolysis of phosphorylated sugar lactones","volume":"51","author":"DF Xiang","year":"2012","journal-title":"Biochemistry"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"SF Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"17540","DOI":"10.1021\/ja2060319","article-title":"Bifunctional triterpene\/sesquarterpene cyclase: tetraprenyl-beta-curcumene cyclase is also squalene cyclase in Bacillus megaterium","volume":"133","author":"T Sato","year":"2011","journal-title":"J Am Chem Soc"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"9734","DOI":"10.1021\/ja203779h","article-title":"Sesquarterpenes (C35 terpenes) biosynthesized via the cyclization of a linear C35 isoprenoid by a tetraprenyl-beta-curcumene synthase and a tetraprenyl-beta-curcumene cyclase: identification of a new terpene cyclase","volume":"133","author":"T Sato","year":"2011","journal-title":"J Am Chem Soc"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/S0014-5793(01)03153-2","article-title":"Bicyclic triterpenes as new main products of squalene-hopene cyclase by mutation at conserved tyrosine residues","volume":"509","author":"C Full","year":"2001","journal-title":"Febs Letters"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1021\/bi052101l","article-title":"Leveraging enzyme structure-function relationships for functional inference and experimental design: The structure-function linkage database","volume":"45","author":"SCH Pegg","year":"2006","journal-title":"Biochemistry"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"2845","DOI":"10.1093\/bioinformatics\/bts532","article-title":"Pythoscape: a framework for generation of large protein similarity networks","volume":"28","author":"AE Barber 2nd","year":"2012","journal-title":"Bioinformatics"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1038\/nprot.2007.324","article-title":"Integration of biological networks and gene expression data using Cytoscape","volume":"2","author":"MS Cline","year":"2007","journal-title":"Nat Protoc"},{"key":"ref76","unstructured":"Schr\u00f6dinger Suite 2011 Protein Preparation Wizard; Epik version 2.2; Impact version 5.7; Prime version 3.0; Jaguar, version 7.9; LigPrep, version 2.5; Glide, version 5.7; Induced Fit Docking protocol."},{"key":"ref77","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1093\/nar\/gkn072","article-title":"PROMALS3D: a tool for multiple protein sequence and structure alignments","volume":"36","author":"J Pei","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0022-2836(02)00470-9","article-title":"On the role of the crystal environment in determining protein side-chain conformations","volume":"320","author":"MP Jacobson","year":"2002","journal-title":"J Mol Biol"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"MP Jacobson","year":"2004","journal-title":"Proteins"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"MY Shen","year":"2006","journal-title":"Protein Sci"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1021\/ja00214a001","article-title":"The Opls Potential Functions for Proteins - Energy Minimizations for Crystals of Cyclic-Peptides and Crambin","volume":"110","author":"WL Jorgensen","year":"1988","journal-title":"J Am Chem Soc"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1002\/jcc.20292","article-title":"Integrated Modeling Program, Applied Chemical Theory (IMPACT)","volume":"26","author":"JL Banks","year":"2005","journal-title":"J Comput Chem"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1002\/qua.24481","article-title":"Jaguar: A high-performance quantum chemistry software program with strengths in life and materials sciences","volume":"113","author":"AD Bochevarov","year":"2013","journal-title":"Int J Quantum Chem"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1016\/j.bmc.2005.12.032","article-title":"New insights about HERG blockade obtained from protein modeling, potential energy mapping, and docking studies","volume":"14","author":"R Farid","year":"2006","journal-title":"Bioorg Med Chem"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"W Sherman","year":"2006","journal-title":"J Med Chem"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"RA Friesner","year":"2004","journal-title":"J Med Chem"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"RA Friesner","year":"2006","journal-title":"J Med Chem"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening","volume":"47","author":"TA Halgren","year":"2004","journal-title":"J Med Chem"},{"key":"ref89","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/prot.22883","article-title":"Estimating binding affinities by docking\/scoring methods using variable protonation states","volume":"79","author":"MS Park","year":"2011","journal-title":"Proteins"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T19:02:40Z","timestamp":1717441360000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1003874"}},"subtitle":[],"editor":[{"given":"Avner","family":"Schlessinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,10,9]]},"references-count":89,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1003874","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,9]]}}}