ClusPro an automated docking and discrimination method for ….pptVIP

ClusPro: an automated docking and discrimination method for the prediction of protein complexes Stephen R. Comeau, David W.Gatchell, Sandor Vajda, and Carlos J. Camacho Bioinformatics Graduate Program and Department of Biomedical Engineering, Boston University Presentation by: Susan Tang Background Motivation Docking = process of starting with a set of coordinates for two distinct molecules and generating a model of the bound complex Numerous methods which perform protein- protein docking exist today Fourier correlation approach (Ritchie and Kemp, 2000) enabled the generation of billions of possible docked conformation via defined scoring functions Problem: Many false-positives (good surface complementarity) that are far from the native complex Motivation: Need to develop methods to filter and rank the docked conformations such that near-native complexes can be identified ClusPro: an automated, fast rigid-body docking and discrimination algorithm that: 1) Rapidly filters docked conformations 2) Ranks the conformations using clustering of computed pairwise RMSD values Input and Method Outline Part I: Free-Energy Filtering Goal: to identify docked conformations having good surface complementarity by selecting those w/ lowest desolvation and electrostatic energies Surface complementarity is an important criteria due to the observation that proteins tend to bury large surface areas after complex formation Electrostatic and desolvation potentials (capturing the free energy of association) are used independently since different binding mechanisms are governed by different ratios of electrostatic/desolvation contributions 500 structures w/ lowest values of desolvation free energy retained 1500 structures w/lowest electrostatic energy retained Electrostatics more sensitive to small coordinate perturbations ? noisy Cannot combine desolvation and electrostatics due to the noisy behavior of electrostatics potential Part II: Clustering based on Pairwise RMSD By