On Side-Chain Conformational Entropy of Proteins 英文参考文献.docVIP

OnSide-ChainConformationalEntropy ofProteins Jinfeng Zhang, Jun S.Liu* DepartmentofStatistics,HarvardUniversity,Cambridge,Massachusetts,UnitedStatesofAmerica Theroleofside-chainentropy(SCE)inproteinfoldinghaslongbeenspeculatedaboutbutisstillnotfullyunderstood. UtilizinganewlydevelopedMonteCarlomethod,weconductedasystematicinvestigationofhowtheSCErelatesto thesizeoftheproteinandhowitdiffersamongaprotein’sX-ray,NMR,anddecoystructures.WeestimatedtheSCEfor a set of 675 nonhomologous proteins, and observed that there is a significant SCE for both exposed and buried residuesforalltheseproteins—thecontributionofburiedresiduesapproaches;40%oftheoverallSCE.Furthermore, the SCE can be quite different for structures with similar compactness or even similar conformations. As a striking example, we found that proteins’ X-ray structures appear to pack more ‘‘cleverly’’ than their NMR or decoy counterpartsinthesenseofretaininghigherSCEwhileachievingcomparablecompactness,whichsuggeststhatthe SCEplays an importantrole in favouringnative proteinstructures. Byincluding aSCEterm in asimple freeenergy function,wecansignificantlyimprovethediscriminationofnativeproteinstructuresfromdecoys. Citation:ZhangJ,LiuJS(2006)Onside-chainconformationalentropyofproteins.PLoSComputBiol2(12):e168.doi:10.1371/journal.pcbi.0020168 proteins are selected under requirements that they have no missingresidues;theirstructural resolutions arebetterthan Introduction 1.6 A;? and no pairs have more than 20% sequence identity. The largest protein in the set has 839 residues. Figure 1A plotstheSCEofproteinsversustheirchainlengths,showing thattheSCEincreasesnearlylinearlywiththechainlength.It alsodemonstratesthattheSCEcomputationisinsensitiveto theuseoftwodifferentscalesforatomradius(seeMethods). Furthermore,weestimatedeachindividualresidue’smarginal SCE based on our weighted Monte Carlo samples, and observed that the fraction of SCE contributed by all the buriedresidues(de?nedastheonewithlessthan25%ofits surface