BIOINFORMATICS 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