lecture19_S2009

lecture19_S2009 - April 22 nd 2009 18.417 Lecture 20...

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Unformatted text preview: April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 1/49 18.417: Comparative modeling and side-chain packing Charles W. O’Donnell Slides courtesty Jérôme Waldispühl, Jinbo Xu (TTI Chicago) April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 2/49 August 8 th , 2008 Science Bradley, et al, Proteins (2003) Bradley, et al, Proteins (2003) April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 3/49 Predictive accuracy slowing increasing April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 4/49 Distance between 3D structures April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 5/49 CASP/CAFASP • CASP: C ritical A ssessment of S tructure P rediction • CAFASP: C ritical A ssessment of F ully A utomated S tructure P rediction CASP Predictor CAFASP Predictor 1. Won’t get tired 2. High-throughput April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 6/49 CASP/CAFASP • Public – Organized by structure community – Evaluated by the unbiased third-party – Held every two years • Blind – Experimental structures to be determined by structure centers after competition • Drawback: <100 targets – Blindness – Some centers are reluctant to release their structures April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 7/49 April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 8/49 Test Protein Category • New Fold (NF) targets – No similar fold in PDB • Homology Modeling (HM) targets – Easy HM: has a homologous protein in PDB – Hard HM: has a distant homologous protein in PDB – Also called Comparative Modeling (CM) targets • Fold Recognition (FR) targets – Has a similar fold in PDB April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 9/49 Protein Structure Prediction • Stage 1: Backbone Prediction – Ab initio folding – Homology modeling – Protein threading • Stage 2: Loop Modeling • Stage 3: Side- Chain Packing • Stage 4: Structure Refinement The picture is adapted from http://www.cs.ucdavis.edu/~koehl/ProModel/fillgap.html April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 10/49 Protein Structure Prediction • Stage 1: Backbone Prediction – Ab initio folding – Homology modeling – Protein threading • Stage 2: Loop Modeling • Stage 3: Side- Chain Packing • Stage 4: Structure Refinement The picture is adapted from http://www.cs.ucdavis.edu/~koehl/ProModel/fillgap.html April 22 nd , 2009 18.417 Lecture 20: Comparative modeling and side-chain packing 11/49 Ab initio Prediction • Sampling the global conformation space – Lattice models / Discrete-state models – Molecular Dynamics – Pre-set libraries of fragment 3D motifs • Picking native conformations with an energy function – Solvation model: how protein interacts with water...
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This note was uploaded on 06/16/2011 for the course MATH 18.417 taught by Professor Jérômewaldispühl during the Spring '11 term at MIT.

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lecture19_S2009 - April 22 nd 2009 18.417 Lecture 20...

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