Protein Structure - Geometry, Topology and Structure下载

I Introduction 6 1 Prologue 7 1.1 ScopeandAims............................ 7 1.2 WhyProteins? ............................ 8 1.2.1 CatchingaDemon ...................... 8 1.2.2 Origins............................. 8 1.3 OutlineoftheWork ......................... 11 2 Basic Principles of Protein Structure 12 2.1 Theshapesandsizesofproteins................... 12 2.1.1 Fibrousproteins........................ 13 2.1.2 Globularproteins....................... 13 2.1.3 Membraneproteins...................... 13 2.2 Thehydrophobiccore......................... 14 2.3 Secondarystructure.......................... 14 2.4 Packedlayers ............................. 16 2.4.1 All-α proteins......................... 16 2.4.2 All-β proteins......................... 16 2.4.3 α-β proteins.......................... 17 2.5 Barrel structures and β-helices.................... 17 2.6 ProteinTopology........................... 19 2.7 Domainstructure........................... 19 II Protein Structure Comparison and Classification 23 3 Overview of Comparison Methods 24 3.1 ChallengesforStructureComparisonMethods........... 24 3.2 DegreesofDi?culty ......................... 25 3.3 Di?erentApproaches......................... 26 3.3.1 ComparisonPower ...................... 26 3.3.2 FeatureorRelationship.................... 26 3.3.3 Hybridmethods........................ 27 3.4 DynamicProgramming........................ 27 3.4.1 Thebasicevolutionarymodel ................ 27 3.4.2 SequenceAlignment ..................... 29 3.4.3 Gap-penalty.......................... 29 3.4.4 StructureBiasedGap-penalties ............... 31 2 4 Early and Simple Approaches 31 4.0.5 Manualandsemi-automaticmethods............ 32 4.0.6 Fragmentbasedmethods................... 32 4.1 ComparingFeatureStrings...................... 33 4.1.1 Residuelevel ......................... 33 4.1.2 Backbone-fragmentlevel................... 34 4.1.3 Secondarystructurelevel................... 34 5 3D Methods without dynamic programming 34 5.1 Distance-matrixmatching ...................... 35 5.1.1 Earlyattempts ........................ 35 5.1.2 The DALI method....................... 36 5.1.3 Backbonefragmentmethods................. 36 5.2 Secondarystructuregraph-matching ................ 37 5.3 Geometric-hashingapproach..................... 38 6 3D Methods using Dynamic Programming 40 6.1 Usingstructuralsuperposition.................... 40 6.2 Usingtherelationshipsofinternalfeatures............. 41 6.2.1 The COMPARER program.................... 41 6.2.2 The SSAP program ...................... 42 6.3 IteratedDoubleDynamicProgramming............... 44 6.3.1 DoubleDynamicProgramming ............... 44 6.3.2 SelectionandIteration.................... 45 6.3.3 Samplingalternatealignments................ 45 7 Assessment of Significance 47 7.1 Scoredistributionsfromknownstructures ............. 47 7.2 Randomstructuralmodels...................... 48 7.3 Randomsedalignmentmodels .................... 48 7.4 Scoringandbiologicalsignificance.................. 49 7.5 Examples ............................... 50 7.5.1 Distantglobinsimilarities .................. 50 7.5.2 Assessment against chain reversal model .......... 52 8 Protein Structure Classification 54 8.1 Introduction.............................. 54 8.1.1 Practicalapplications..................... 54 8.1.2 Genomeappliactions..................... 55 8.2 Practicalapproachestoclassification ................ 55 8.2.1 Automatedapproachestoclassification........... 56 8.3 Organisationoftheclassifications.................. 57 8.3.1 Theunitofclassification................... 57 3 8.3.2 Hierarchicalorganisation................... 57 8.3.3 Hierarchicalclassification................... 58 8.4 RemainingProblems ......................... 58 8.4.1 What questions does classification help us to answer? . . . 58 8.4.2 Questionsraisedbyclassification .............. 59 8.4.3 Futureprospects ....................... 60 III Geometric Abstractions and Topology 61 9 Simplified Geometries 62 9.1 StructureRepresentations ...................... 62 9.1.1 Frombondstocartoons ................... 62 9.1.2 From3-Dto2-D ....................... 62 10 Stick Representation 64 10.1Secondarystructureline-segments.................. 64 10.1.1Problemswithcurrentcriteria................ 64 10.1.2Linesegmentsfrominertialaxes............... 65 10.1.3Dynamicprogrammingsolution............... 66 10.1.4‘Continuous’secondarystructuretypes........... 67 11 Ideal Forms 67 11.1LayerArchitectures.......................... 70 11.1.1 α/β/α layers ......................... 70 11.1.2 β/β layers........................... 71 11.1.3 β/α-barrelproteins...................... 71 11.1.4 All-α proteins......................... 71 11.1.5Transmembranemodels ................... 71 11.2Stick-figurecomparisons ....................... 73 11.2.1AngleandDistancematching ................ 73 11.2.2Findingthebestmatch.................... 73 11.2.3 Evaluation using SAP ..................... 76 11.2.4Nestedsolutions........................ 76 11.3Classificationusingidealstickforms................. 78 11.3.1Aperiodictableofproteins ................. 78 12 Fold Combinatorics 80 12.0.2Motifincorporation...................... 80 12.1Evaluatingfolds............................ 81 4 13 Protein Topology 84 13.1Introduction.............................. 84 13.2Chemicaltopology .......................... 84 13.3Polymertopology........................... 85 13.3.1Bonddirection ........................ 86 13.3.2Linearpolymers........................ 86 13.3.3Branchingpolymers...................... 86 13.3.4Circularpolymers....................... 86 13.4TrueTopologyofProteins ...................... 87 13.4.1Disulfidebridges ....................... 87 13.4.2Othercross-links ....................... 89 13.5Pseudo-TopologyofProteins..................... 89 13.5.1Topologyofweaklinksinproteins.............. 89 13.5.2Topologyof‘circular’proteins................ 90 13.5.3‘Topology’ofopenchains .................. 91 14 Symmetry 97 14.1Structuraloriginsoffoldsymmetries ................ 97 14.1.1 βα-class............................ 97 14.1.2 ββ-class ............................ 97 14.1.3 αα-class............................ 98 14.2Evolutionaryoriginsoffoldsymmetries............... 98 14.3Conclusions .............................. 100