Thisstudyexplorestheuseofmultiplesequencealignment (MSA)informationand globalmeasuresofhydrophobiccoreformationfor improvingtheRosettaabinitioproteinstructure predictionmethod.Themosteffectiveuseofthe MSAinformationisachievedbycarryingoutindependentfoldingsimulationsforasubsetofthe homologoussequencesintheMSAandthenidentifyingthefreeenergyminimacommontoallfolded sequencesviasimultaneousclusteringoftheindependentfoldingruns. Globalmeasuresofhydrophobiccoreformation, usingellipsoidalratherthan sphericalrepresentationsofthehydrophobiccore, arefoundtobeusefulinremovingnon-nativeconformationsbeforeclusteranalysis. ThroughthiscombinationofMSAinformationandglobalmeasuresof proteincoreformation,wesignificantlyincrease theperformanceofRosettaonachallengingtestset. Proteins2001;43:1--11.2001Wiley-Liss,Inc.

The re3R3 ofthe se00 Critical AssecalRfi of FullyAutomate Structure Prectu tion (CAFASP2)are preP2)R0H The goals of CAFASP are to (i)asse0 the pe0"3NRvH of fully automatic we setoma forstructure preturevH by usingthe same blindpreR0fiN"I targe0 asthose use at CASP4, (ii) informthe community ofuse1 aboutthe capabilitie ofthe seU3IR (iii) allow human groups participating in CASP touse andanalyze the reyze ofthe se"I0R while preeRv1 thee nonautomate preautomat for CASP, and (iv)compare the peare mance ofthe automate seomat to that ofthe humaneuman groups of CASP.More than 30sefi1I" from aroundthe world participate in CAFASP2,coveP ing all cate""Rv1 ofstructure preture13 The cateat - withthe largefi participation was foldredRfi nition,when 24 CAFASP seASPR file prePR0UU"" along with 103othe CASP human groups.The CAFASPeSPR00H13 indicate that it is difficult to eoRfiINHU aneR01 ranking ofthe se3"I be3"I the numbe of preU0RvfiH targe0 was refi"03"Rv small andthe diffeU3Rvfi among manyseyRfiH wey also small.HoweR0fi roughly a group offive "be"3 fold reRIH10Rvfi seeH1 couldbe ideRfi010H The CASP eR03fi3IRv ide3fi3I the same group of top sepRfiI albeI with a slightly diffelyR refely orde - Both ehR0fi01fiRv ranke a se"30Rv0U300 mee" name CAFASP-CONSENSUS, that file pre dictions usingthe CAFASP reASPR ofthe seHfiHI above any ofthe individualsedivid Althoughthe preoughRfiN ofthe CAFASP seASPR weA available to human CASPpre01"NfiR bee0 the CASP submissiondenRI ""1 the CASPasseU01fiR ideeU01 only 11 human groups thatpetR0N"H betR0 thanthe beh seheR FurtheI""Rv aboutone fourth ofthe top 30 pe"IHRvUU groupscorre0I1N"R to automate se-RfiI Atle0" half ofthe top 11 groups correRfiINHN to human gr...

Research article Structural model of nicotinic acetylcholine receptor isotypes bound to acetylcholine and nicotine

Research article Exploring dynamics of protein structure determination and homology-based prediction to estimate the number of superfamilies and folds

sites of known enzyme structures, the comparison and alignment of protein structures has come to be a fundamental and widely used task in computational structure biology. Three main steps are needed for comparing two protein structures: first, the detection of their

ABSTRACT The results of the second Critical

ABSTRACT Thisstudyexplorestheuseofmultiple sequence alignment (MSA) information and global measures of hydrophobic core formation for improving the Rosetta ab initio protein structure prediction method. The most effective use of the MSA information is achieved by carrying out independent folding simulations for a subset of the homologoussequencesintheMSAandthenidentifying the free energy minima common to all folded sequences via simultaneous clustering of the independentfoldingruns.Globalmeasuresofhydrophobic core formation, using ellipsoidal rather than spherical representations of the hydrophobic core, arefoundtobeusefulinremovingnon-nativeconformationsbeforeclusteranalysis.Throughthiscombination of MSA information and global measures of protein core formation, we significantly increase theperformanceofRosettaonachallengingtestset. Proteins2001;43:1–11. ©2001Wiley-Liss,Inc. Key words: ab initio structure prediction; homology;Rosetta