Table of ContentsBIOINFORMATICS Structures Contents: Structures Molecular Biology Information: Macromolecular Structure Molecular Biology Information: Protein Structure Details Other Aspects of Structure, Besides just Comparing Atom Positions What is Protein Geometry? Depicting Protein Structure: Sperm Whale Myoglobin Incredulase Structure alignment - Method Sperm Whale Myoglobin Structural Alignment of Two Globins Automatic Alignment to Build Fold Library Automatically Comparing Protein Structures RMS Superposition (1) RMS Superposition (2): Distance Between an Atom in 2 Structures RMS Superposition (3): RMS Distance Between Aligned Atoms in 2 Structures RMS Superposition (4): Rigid-Body Rotation and Translation of One Structure (B) RMS Superposition (5): Optimal Movement of One Structure to Minimize the RMS Alignment (1) Make a Similarity Matrix (Like Dot Plot) Structural Alignment (1b) Make a Similarity Matrix (Generalized Similarity Matrix) Structural Alignment (1c*) Similarity Matrix for Structural Alignment Alignment (2): Dynamic Programming, Start Computing the Sum Matrix Alignment (3):Dynamic Programming, Keep Going Alignment (4): Dynamic Programming, Sum Matrix All Done Alignment (5): Traceback In Structural Alignment, Not Yet Done (Step 6*) Structural Alignment (7*), Iterate Until Convergence Structure alignment - Scoring Score S at End Just Like SW Score, but also have final RMS Some Similarities are Readily Apparent others are more Subtle Some Similarities are Readily Apparent others are more Subtle P-values Statistics on Range of Similarities Scores from Structural Alignment Distributed Just Like Ones from Sequence Alignment (E.V.D.) Same Results for Sequence & Structure Score Significance (P-value) derived from Extreme Value Distribution (just like BLAST, FASTA) RMS is a similarity Score Structure alignment - Other methods Refine Method Significance Ignoring Crucial Features in Structural Similarity Other Methods of Structural Alignment Fold Library vs. Other Fundamental Data structures Fold Classifications Sequence-structure Relationships Adding Structure to Functional Genomics, Function to Structural Genomics Chothia & Lesk, 1986 -- 32 points Chothia and Lesk, revisited 16K points Problems with RMS Structural Comp. Score vs.Smith-Waterman Score Problems with Structural Alignment Score Modern statistical language Focus on Twilight Zone Hierarchy of Protein Functions Relationship of Similarity in Sequence & Structure to that in Function Relationship of Similarity in Sequence & Structure, & Function - Summary Surfaces I Protein Surfaces -- Accessible Surface Molecular Surface Richards’ Molecular and Accessible Surfaces How to Calculate Accessible Surface Area Shrake & Rupley algorithm (easier) Calculation of Volumes Voronoi Volumes Classic Papers Calculating Volumes with Voronoi polyhedra Determining Voronoi Volumes Collecting Vertices and Calculating Volumes Atoms have different sizes Complexity from different atom sizes requires new ways to calculate polyhedra Representing Lines, Planes, and their Intersection PPT Slide Delauney Triangulation, the Natural Way to Define Packing Neighbors Properties of Voronoi Polyhedra Voronoi diagrams are generally useful, beyond proteins Voronoi Volumes & Packing Voronoi Volumes, the Natural Way to Measure Packing Close-Packing of Spheres Other Well Known Sphere Arrangements Optimal Packing Finally Proved Water v. Argon Small Packing Changes Significant Packing ~ VDW force Close-packing is Default Standard Radii & Volumes Different Sets of Radii ProtOr Parameter Set Factors Affecting Volume Calculations Set of VDW Radii Standard Residue Volumes Standard Core Volumes (Prelim.) Clustering into a set of Atom Types I Clustering into a set of Atom Types II Compare Different Structure Sets Overlap of Volumes of Aromatic C3H1 and Aliphatic C4H2 Surfaces II Packing at Interfaces Packing defines the “Correct Definition” of the Protein Surface Surface and Volume Definitions Linked Problem of Protein Surface for Voronoi Construction Sensitivity of Voronoi Construction to Surface Structure Hydration Surface Defining Surfaces from Packing: Convex Hull and Layers of Waters Defining a Surface from the Faces of Voronoi Polyhedra Accessible Surface as a Time-averaged Water Layer The Hydration Surface: Trying to Model Real Water Other Applications of Volumes -- Motions, Docking Interface Packing and Motions Packing Based Classification: Hinge v Shear Absence of Tight Packing at Hinge Chain Topology is not important Docking |
Author: Office97
Email: Mark.Gerstein@yale.edu Home Page: http://bioinfo.mbb.yale.edu |