Applications of Potential Energy Surfaces in the Study of Enzymatic Reactions英文文献资料.docVIP

HindawiPublishingCorporation AdvancesinPhysicalChemistry Volume2012,ArticleID867409,15pages doi:10.1155/2012/867409 ReviewArticle ApplicationsofPotentialEnergySurfacesintheStudyof EnzymaticReactions EricA.C.Bushnell,WenJuanHuang,andJamesW.Gauld DepartmentofChemistryandBiochemistry,UniversityofWindsor,Windsor,ON,CanadaN9B3P4 CorrespondenceshouldbeaddressedtoJamesW.Gauld,gauld@uwindsor.ca Received26June2011;Revised23August2011;Accepted29August2011 AcademicEditor:LaimutisBytautas Copyright?2012EricA.C.Bushnelletal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttribution License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly cited. FromageneratedPES,onecandeterminetherelativeenergiesofspeciesinvolved,thesequenceinwhichtheyoccur,andthe activationbarrier(s)associatedwithindividualstepsortheoverallmechanism.Furthermore,theycanprovidemoreinsightsthan asimpleindicationofapathofsequentialmechanisticstructuresandtheirenergeticrelationships.Theinvestigationintothe activationofO2 byalpha-ketoglutarate-dependentdioxygenase(AlkB)clearlyshowstheopportunityforspininversion,where onecanseethatthelowestenergyproductmaybeformedviaseveralpossibleroutes.Intheinvestigationofuroporphyrinogen decarboxylase III (UROD), the use of QM/MM methods allowed for the inclusion of the anisotropic protein environment providinggreaterinsightintotherate-limitingbarrier.Lastly,themechanismof6-phospho-α-glucosidase(GlvA)wasdiscussed usingdi?erentactivesitemodels.Inparticular,acontinuummodelPESwascomparedtothegas-phasePES. 1.Introduction Theuseandapplicabilityofsuch“reduced-dimension- ality” PESs re?ects the fact that chemists and biochemists are usually only interested in key, mechanistically relevant structuresincluding,forexample,the(i)isolatedreactants, (ii) reactive complex, (iii) transition structures (TS), (iv) intermediate(s),(v)productcomplex,and(vi)theseparated products(Figure1)[1].Itisnotedthatingeneral,compu- tationalstudie