Monte Carlo simulation of the kinetics of protein adsorption

Abstract

Adsorption of proteins occurs via diffusion toward the interface, actual adsorption, and subsequent irreversible conformational changes resulting in denaturation of the native protein structure. The conventional kinetic models describing these steps are based on the assumption that the denaturation transitions obey the first-order law with a single value of the denaturation rate constant kr. Meanwhile, recent Monte Carlo simulations indicate that, in general, the denaturation process cannot be described by a single rate constant kr. One should rather introduce a distribution of this rate constant (physically, different values of kr correspond to the transitions to the altered state via different metastable states). We have calculated the kinetics of irreversible adsorption of proteins with and without distribution of the denaturation rate constant kr in the limits when protein diffusion in the solution is, respectively, rapid or slow. In both cases, the adsorption kinetics with distribution of kr are found to be close to those with a single-valued rate constant kr provided that the average value of kr in the former case is equal to kr for the latter case. This conclusion holds even for wide distributions of kr. The consequences of this finding for the fitting of global experimental kinetics on the basis of phenomenological equations are briefly discussed. Proteins 30:177–182, 1998. © 1998 Wiley-Liss, Inc.