Fall 2006 Seminar Series

DATE: Thursday, November 30, 2006
LOCATION: E40-298
TIME: 4:15pm
Reception immediately following in the Philip M. Morse Reading Room, E40-106

SPEAKER:
Yannis Paschalidis

TITLE
Optimization for Protein-Protein Docking

ABSTRACT
I shall present our recent work motivated by a fundamental and challenging problem in computational structural biology. Protein-protein interactions play a central role in metabolic control, signal transduction, and gene regulation. Determining the 3-dimensional (3D) structure of a complex from the atomic coordinates of two interacting proteins (the receptor and the ligand) is known as the protein-protein docking problem. Experimental techniques can provide such 3D structures but are time-consuming, expensive, and not universally applicable. As a result, solving these problems computationally is critical and has attracted a lot of attention.

 

Nature being efficient, protein-protein docking can be formulated as a the problem of minimizing the Gibbs free energy of the complex. Optimization is performed over translations (R^3) and rotations (the rotation group SO(3)) of the ligand with respect to the receptor as well as over conformational changes (especially side-chains at the interface). However, the free-energy functional is very complex having multiple deep funnels and a huge number of local minima of less depth that are spread over the domain of the function. We present a systematic way of performing this optimization. A key tool to that end is a new stochastic global optimization method we have developed, the so called Semi-Definite programming based Underestimation (SDU) method. The method is based on finding general convex underestimators to the binding energy function that is funnel-like. The underestimator is used to bias sampling in the search region. We provide probabilistic convergence guarantees, comparisons with related work, and an array of computational results illustrating our approach.