Dr. Ron Elber
Department of Chemistry and Biochemistry and
Institute of Computational Sciences and Engineering (ICES)
University of Texas at Austin, TX

Monday, November 15, 2010
3:00 pm (CT)
3269 Beckman Institute

Abstract

Abstract: Milestoning is a method for calculating kinetics and thermodynamics of long time processes typically not accessible for straightforward Molecular Dynamics (MD) simulation (Faradjian and Elber 2004; West, Elber et al. 2007). Among systems investigated one finds the allosteric transition in Scapharca hemoglobin (10 microseconds) (Elber 2007), and the recovery stroke in myosin (milliseconds) (Elber and West 2010). In the Milestoning approach, the system of interest is partitioned into cells by dividing hypersurfaces (Milestones) and transitions are computed between nearby hypersurfaces. Kinetics and thermodynamics are derived from the statistics of these local transitions. Motivated by the Voronoi Tessellation variant of Milestoning of Venturoli and Vanden- Eijnden (Vanden-Eijnden and Venturoli 2009) we describe an extension to the original Milestoning that we called Directional Milestoning. It avoids the use of a reaction coordinate, provides exact first hitting distribution at the interfaces, and supports a sufficiently long relaxation time between the interfaces for better accuracy (Majek and Elber 2010). I will describe the adjusted theory and algorithm, and will present results on a model system alanine dipeptide and for the folding of the helical peptide WAAAH. Interestingly the kinetic of folding of WAAAH shows significant co-operativity and is close to an all or none transition. The calculations are consistent with experimental measurements of kinetic, thermodynamic, and structure of this peptide.