同源模建.pptVIP

February 16th, 2004 (c) CGDN February 16, 2004 Fiona Brinkman (c) 2004 CGDN Protein Structural Analysis and Homology Modeling Lushan Wang 核酸、蛋白质序列分析 —— 一维序列的信息分析 Bioinformatics will help with…….Phylogenetics we can define evolutionary relationships between organisms by comparing DNA sequences Similarity Searching Sequence Databases What is similar to my sequence? Searching gets harder as the databases get bigger - and quality changes Tools: BLAST and FASTA = time saving heuristics (approximate methods) Statistics + informed judgement of the biologist Structural Interactions Bioinformatics experiments: Data to integrate Genomic sequences mRNA sequences Protein sequences Protein structures Protein function Biomolecular interactions Physical Amino Acids andAmino Acid Abstractions The Concept of Abstract Amino Acids Allows Highly Compressed Information The Concept of Abstract Amino Acid Similarity is Lossy Structure Contextualizes Sequence Structural Abstraction To store structures we need: - coordinate - topology, and - chemical type information. Concept 2: Structure can be determined experimentally. Experimental sources of structure X-ray NMR Cryo TEM Experimental sources of structure Experimental sources of structure X-ray NMR Experimental sources of structure Assessing structure quality Metrics: Resolution, R-factor and R-free Bond length and angle deviations Coordinate error can be estimated from diffraction data Concept 3: Structure abstractions can be stored, retrieved and visualized. The PDB What’s in a Structure File? Population experiments X-ray, 1 structure NMR - sometimes many structures Incomplete - not all “atoms” are there Hydrogens, parts of the protein in motion Crystallographic “space” correct, but not always relevant The PDB format Flat file, column oriented Human readable Human editable Huge legacy problems Header Seqres Atom Hetero Atoms PDBsum - and secondary structure databases Geometric relationships Dihedral angles