Structures and Structure DescriptionsProtein ClassesFolding in Globular ProteinsFoldingStructural ComparisonProcessStructure DescriptionCoordinates From NMR or X-Ray CrystallographyDistance MatricesTorsion AnglesLine Segments (sticks)HelicesStrands and SheetsCartoons for Secondary Structure Elements (SSE)Comparing StructuresPairwise ComparisonSlide 17ExampleBut not so with structuresLast Slide Structures and Structure DescriptionsChapter 8 Protein BioinformaticsProtein Classes1.1.ActiveActive – Mobility and catalysis–soluble and globular in shape2.2.PassivePassive – structural3.3.MembraneMembrane – control import and export through membraneFolding in Globular Proteins•fold into compact units •100-1000 nucleotides•Stable fold has minimum energy–Native state•Energy loss occurs when bonds are formed:–H-Bonds–disulfide bridges (cysteine)–metallic bonds w/ metal ionsFoldingFormation of H-bonds:•Hydrophilic amino acids are soluble, hydrophobic are not•To maximize H-bonds, put hydrophilic on the surface so the whole protein is soluble•Causes the formation of the two dominant Secondary Structure Elements (SSEs):1. α-helix2. β-strandStructural Comparison•Fine Level (residue)–used for finding spa tial similarities – active and binding sites–helpful for determining function–done by specifying coordinates, distances, or torsion angles•Coarse Level (SSE)–used for comparing on the global level–helpful for classifying proteins into classe s–done by describing SSEs using line segments or as ellipsoidsProcessStructure Description•ArchitectureArchitecture - position of (or Geometry) elements (atoms or residues)•TopologyTopology - order of elements along the backbone•PropertiesProperties - physio-chemical properties and types of SSEsCoordinatesFrom NMR or X-Ray CrystallographyATOM 1 N PRO A 2 31.242 3.064 39.284 1.00 39.90 N ATOM 2 CA PRO A 2 31.195 2.392 37.963 1.00 31.96 C ATOM 3 C PRO A 2 29.975 2.923 37.197 1.00 30.23 C ATOM 4 O PRO A 2 29.727 4.132 37.181 1.00 27.03 O ATOM 5 CB PRO A 2 31.063 0.905 38.251 1.00 36.57 C ATOM 6 CG PRO A 2 30.276 0.947 39.549 1.00 35.11 C ATOM 7 CD PRO A 2 30.829 2.121 40.343 1.00 42.06 C ATOM 8 N TYR A 3 29.189 2.020 36.613 1.00 22.83 N ATOM 9 CA TYR A 3 28.011 2.405 35.850 1.00 18.42 C ATOM 10 C TYR A 3 26.711 1.995 36.517 1.00 19.46 C ATOM 11 O TYR A 3 26.629 0.949 37.161 1.00 24.89 O ATOM 12 CB TYR A 3 28.055 1.772 34.459 1.00 17.73 CDistance Matrices•Distances can be stored with 3n-6 distances instead of 4n-10 coordinates.•2D representation of the 3D structureTorsion Angles•Angles between two bonds of each atom in the backbone are approx. equal•Freedom comes in rotating around single bonds(-70,-20), (-72,60), (-70,120), (-60,170), (-65, 125), (-100, 45), (-100, -65), (-105, -66), (-100, 60)Line Segments (sticks)•Fit a line to the Catom of each residue by least squaresEllipsoids•Three inertial axeslong axis corresponds to stick representationHelices•α-helix 4-turn helix, min. 4 residues310-helix 3-turn helix, min. 3 residuesπ-helix 5-turn helix, min. 5 residues•Formed by H-Bonds between residues in the same helixStrands and Sheets•Formed by successive H-Bonds between residues can be far apart in sequence.Cartoons for Secondary Structure Elements (SSE)•Topology of Protein Structure (TOPS)–Triangular symbols represent beta strands–Circular symbols represent helices (alpha and 310)–The peptide chain is divided into a number of fragments each labelled with an integer (i), beginning at Ni and ending at Ci+1.–The first fragment is N1->C2 (or N->C).–Each fragment lies in only one structural domain. –Where the chain crosses between domains it leaves the first at Ci and joins the next at Ni.–Each secondary structure element has a direction (N to C) which is either "up" ( out of the plane of the diagram ) or "down" (into the plane of the diagram).Comparing Structures•Structure Representations – pg. 185-186 (11-12 of pdf)–Strings–List of unit descriptions–Set of unit descriptions–Graphs–Feature ArraysPairwise Comparison•Finding equivalence or alignment giving highest score is NP-CompleteExample•Alignment–ACSL-DRTS-IRV–A-TLREKSSLIR-•Know first 5 residues–ACSL-D–A-TLREBut not so with structuresDynamic Programming cannot be used directly for structure alignmenthighest score alignment of entire structureshighest score alignment of first five residuesRCSB PDB - HUMAN GLUTATHIONE S-TRANSFERASELast Slide •Explore pdb and install cn3d•http://www.rcsb.org/pdb•http://www.ncbi.nlm.nih.gov/Structure/CN3
View Full Document
Unlocking...