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CSC Open Day 2008 - Talk abstracts

Single-sweep Methods for Free Energy Calculations

Prof. Eric Vanden Eijnden (Courant Institute, NYU)



The free energy (or potential of mean force) is the thermodynamic force driving structural processes such as conformational changes of macromolecules in aqueous solution, ligand binding at the active site of an enzyme, protein-protein association, etc. The free energy gives information about both the rate at which these processes occur and the mechanism by which they occur. This makes free energy calculations a central issue in biophysics. Molecular dynamics (MD) simulations provide a tool for performing such calculations on a computer in a way which is potentially both precise and inexpensive. Since a free energy is proportional to the logarithm of a probability density function it can in principle be calculated by histogram methods based on the binning of an MD trajectory. This direct approach, however, turns out to be unpractical in general because the time scale required for the trajectory to explore all the relevant regions of configuration space is prohibitively long. In this talk, I will present a new approach to map multi-dimensional free energy landscapes. The method uses radial-basis functions to represent the free energy and is based on a variational approach to reconstruct the free energy globally from the mean force estimated at a few locations in the free energy landscape. The method will be illustrated on the several examples and will be shown to be much more efficient than existing techniques based on histogram methods such as WHAM or metadynamics.