Professor Peter C. Jordan
Department of Chemistry
Brandeis University
Waltham, MA

Monday, December 7, 2009
3:00 pm (CT)
3269 Beckman Institute

Abstract

Normal Mode Analysis (NMA) is a powerful tool for identifying and illuminating the cooperative motions governing conformational change in macromolecules [1]. Using traditional and enhanced methods, I discuss aspects of our studies of large-scale conformational transitions (gating) in five representative systems: the model channel gramicidin A, the potassium selective ion channel KcsA, the galactoside symporter lactose permease, the neurotransmitter LeuTAa, and the chloride selective antiporter ClC-ec1. The insights gleaned may have general physiological applicability. The focus is on systems where only one stable conformation has been structurally characterized. The results yield a number of important observations: 1. Confirmation of the well-know observation that biomolecular shape dictates the character of the lowest frequency cooperative motions in protein assemblies. 2. Demonstration that standard NMA provides an uncertain guide for characterizing large-scale conformational transitions in proteins. 3. Demonstration that the enhanced methods accurately characterize the transitions occurring during the gating process, and provide a way to identify biomolecular conformations of saddle points and subsidiary minima. 4. Demonstration that only all-atom methods reliably account for detailed influence of quaternary structure on conformational transitions.

2:30 pm: Coffee hour Theoretical and Computational Biophysics Group area, 3rd Floor Beckman