Variations in the Fast Folding Rates of the λ-Repressor: A Hybrid Molecular Dynamics Study

Abstract

The ability to predict the effects of mutations on protein folding rates and mechanisms would greatly facilitate folding studies. Using a realistic full atom potential coupled with a Gō-like potential biased to the native state structure, we have investigated the effects of point mutations on the folding rates of a small single domain protein. The hybrid potential provides a detailed level of description of the folding mechanism that we correlate to features of the folding energy landscapes of fast and slow mutants of an 80-residue-long fragment of the λ-repressor. Our computational reconstruction of the folding events is compared to the recent experimental results of W. Y. Yang and M. Gruebele (see companion article) and T. G. Oas and co-workers on the λ-repressor, and helps to clarify the differences observed in the folding mechanisms of the various mutants.