FOLDING AND MISFOLDING OF DESIGNED PROTEINLIKE CHAINS WITH MUTATIONS

We study the impact of mutations (changes in amino acid sequence) on t he thermodynamics of simple proteinlike heteropolymers consisting of N monomers, representing the amino acid sequence. The sequence is desig ned to fold into its native conformation on a cubic lattice. It is fou nd that quite a large fraction, between one-half and one-third of the substitutions, which we call ''cold errors,'' make important contribut ions to the dynamics of the folding process, increasing folding times typically by a factor of 2, the altered chain still folding into the n ative structure. Few mutations (''hot errors''), have quite dramatic e ffects, leading to protein misfolding. Our analysis reveals that mutat ions affect primarily the energetics of the native conformation and to a much lesser extent the ensemble of unfolded conformations, corrobor ating the utility of the ''energy gap'' concept for the analysis of fo lding properties of proteinlike heteropolymers. (C) 1998 American Inst itute of Physics.