Unfolding of globular proteins: monte carlo dynamics of a realistic reduced model.
Reduced lattice models of proteins and Monte Carlo dynamics were used to simulate the initial stages of the unfolding of several proteins of various structural types, and the results were compared to experiment. The models semiquantitatively reproduce the approximate order of events of unfolding as well as subtle mutation effects and effects resulting from differences in sequences of similar folds. The short-time mobility of particular residues, observed in simulations, correlates with the crystallographic temperature factor. The main factor controlling unfolding is the native state topology, with sequence playing a less important role. The correlation with various experiments, especially for sequence-specific effects, strongly suggests that properly designed reduced models of proteins can be used for qualitative studies (or prediction) of protein unfolding pathways.
Kolinski
Andrzej
A
Laboratory of Theory of Biopolymers, Faculty of Chemistry, Warsaw University, Warsaw, Poland. skolnick@buffalo.edu
Klein
Piotr
P
Romiszowski
Piotr
P
Skolnick
Jeffrey
J
D001059:Apoproteins / Q000737:chemistry; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry; D007874:Leghemoglobin / Q000737:chemistry; D008956:Models, Chemical; D008958:Models, Molecular; D015233:Models, Statistical; D009010:Monte Carlo Method; D009211:Myoglobin / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010970:Plastocyanin / Q000737:chemistry; D011489:Protein Denaturation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*
D001059:Apoproteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C029152:G-substrate; C116593:L-protein, Peptococcus magnus; D007874:Leghemoglobin; D009211:Myoglobin; D009419:Nerve Tissue Proteins; D011506:Proteins; C010857:apomyoglobin; D010970:Plastocyanin