111405 Protein StructurePrediction amp; ModelingProtein-nucl.ppt

11/14/05 D Dobbs ISU - BCB 444/544X: Protein Structure Prediction - cont. 11/14/05 Protein Structure Prediction - cont. D Dobbs ISU - BCB 444/544X 11/14/05 Protein StructurePrediction ModelingProtein-nucleic acid interactions; protein-ligand docking(no time, sorry!)  Bioinformatics Seminars Bioinformatics Seminars Protein Structure PredictionGenome Analysis Mon Protein 3 structure prediction Wed Genome analysis genome projects Comparative genomics; ENCODE, SNPs, HapMaps, medical genomics Thur Lab Protein structure prediction Fri Experimental approaches: microarrays, proteomics, metabolomics, chemical genomics Reading Assignment (for Mon-Fri) Mount Bioinformatics Chp 11 Genome Analysis /ch/ch11/index.html pp. 495 - 547 Ck Errata: /help/errata2.html BCB 544 Additional Readings Review last lecture: Protein Structure Predictionfocus on:Tertiary Structure Structural Genomics ~ 30,000 traditional genes in human genome (not counting alternative splicing, miRNAs) ~ 3,000 proteins expressed in a typical cell Structural Genomics Projects Major unsolved problem in molecular biology In cells: spontaneous assisted by enzymes assisted by chaperones In vitro: many proteins fold spontaneously many do not! Deciphering the Protein Folding Code Protein Structure Determination? High-resolution structure determination X-ray crystallography (1A?) Nuclear magnetic resonance (NMR) (~1-2.5A?) Lower-resolution structure determination Cryo-EM (electron-microscropy) ~10-15A? Theoretical Models? Highly variable - now, some equiv to X-ray! Tertiary Structure Prediction Fold or tertiary structure prediction problem can be formulated as a search for minimum energy conformation search space is defined by psi/phi angles of backbone and side-chain rotamers search space is enormous even for small proteins! number of local minima increases exponentially of the number