Variations in the fast folding rates of the lambda-repressor: a hybrid molecular dynamics study.
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 lambda-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 lambda-repressor, and helps to clarify the differences observed in the folding mechanisms of the various mutants.
Pogorelov
Taras V
TV
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, 61801, USA.
Luthey-Schulten
Zaida
Z
D000465:Algorithms; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D009154:Mutation / Q000235:genetics*; D017510:Protein Folding; D012097:Repressor Proteins / Q000737:chemistry*; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins