MONTE-CARLO SIMULATION OF DENATURATION OF ADSORBED PROTEINS

Denaturation of model proteinlike molecules at the liquid-solid interf ace is simulated over a wide temperature range by employing the lattic e Monte Carlo technique. Initially, the molecule containing 27 monomer s of two types (A and B) is assumed to be adsorbed in the native folde d state (a 3 x 3 x 3 cube) so that one of its sides is in contact with the surface, The details of the denaturation kinetics are found to be slightly dependent on the choice of the side, but tile main qualitati ve conclusions hold for all the sides, In particular; the kinetics obe y approximately the conventional first-order law at T > T-c (T-c is th e collapse temperature for solution), With decreasing temperature, bel ow T-c but above T-c (T-c is the folding temperature for solution), de viations appear from the first-order kinetics. For the most interestin g temperatures, that is, below T-f, the denaturation kinetics are show n to be qualitatively different from the conventional ones. In particu lar the denaturation process occurs via several intermediate steps due to trapping in metastable states. Mathematically, this means that (i) the transition to the denatured state of a given molecule is nonexpon ential, and (ii) the denaturation process cannot be described by a sin gle rate constant k(r). One should rather introduce a distribution of values of this rate constant (different values of k(r) correspond to t he transitions to the altered state via different metastable states). (C) 1998 Wiley-Liss, Inc.