Computer Simulations of Molecular Recognition in Antibody- Protein Association

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The principal theoretical methodology proposed here is Brownian dynamics (BD). The basic idea in Brownian dynamics simulations is to model the complexation of two proteins undergoing relative motion according to Brownian motion under the influence of interprotein forces. The forces are often electrostatic in origin and continuum approaches such as the Poisson-Boltzmann (PB) method have been employed. In most BD calculations, the associating proteins have been described by simple models and while this has yielded qualitatively correct results, it has been difficult to predict absolute association rate constants. Also, only simple models of hydrodynamic interactions have been considered. We propose here to a) develop a detailed residue-level model for substrate/target and b) incorporate more accurate hydrodynamic effects into the method. It is increasingly recognized that simulations would serve as a valuable companion to experimental investigations and we want to establish the validity of Brownian dynamics as a useful method for studying kinetics of macromolecular association.