UNCC College of Computing and Informatics

Graduate Seminar (2008 Spring)

Title: Mind your P’s and Q’s: A fast algorithm for predicting protein stability

Donald J. Jacobs, Ph.D

Assistant Professor of Physics

Department of Physics and Optical Science

University of North Carolina at Charlotte

April 18 at 3:00pm
106 Woodward

Abstract:

Proteins have many noncovalent interactions that determine their three-dimensional structure and stability. An open challenge is to develop a computational method that accurately predicts protein thermodynamics and flexibility for specified solvent and thermodynamic conditions in computing times fast enough for protein design applications. Central to this task is to reconcile conformational flexibility as a critical link relating structure to stability. After discussing basic principles of structural biology, mechanics of networks and physical chemistry, a Distance Constraint Model (DCM) is defined based on a paradigm that combines constraint theory with free energy decomposition. In prior work, the DCM is solved using an efficient graph-rigidity algorithm in conjunction with a hybrid Monte Carlo and mean field approximation (MFA). Recent developments will be presented on how the DCM is extended to better account for solvent effects, and solved more accurately using a self-consistent MFA. The calculations remain fast by employing a new type of graph-rigidity algorithm. Results for a prototype two-dimensional lattice model for protein structure demonstrates feasibility for real proteins. It is projected that the free energy of a 1000 residue protein can be calculated in a few minutes with parallelization on a modest high performance cluster.

Bio:

Dr. Donald Jacobs joined the Department of Physics and Optical Science at UNC Charlotte in 2005. In 1992, he received his Ph.D. in physics from Purdue University, concentrating in computational and statistical physics. His Ph.D. thesis was on Brownian motion in disordered media. He had a post doctoral fellowship at the Institute of Theoretical Physics, University of Utrecht in the Netherlands, where he studied dynamics of phase separating binary fluid mixtures using cellular automata lattice gas models. In 1994, he was a research associate, and later a Research Assistant Professor at Michigan State University, where he studied amorphous glass networks. During that time, he worked on topics related to rigidity percolation, and developed algorithms to decompose a molecular network into rigid and flexible parts. Dr. Jacobs patented his rigidity algorithm, applied it to study protein flexibility, and formed the company MolFlex. In 1999, he joined the Department of Physics and Astronomy at California State University, Northridge where he took the lead role in developing a biomedical physics program. Since arriving at UNC Charlotte, he has two patents pending related to novel algorithms for calculating protein thermodynamics.

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