Do homologous thermophilic-mesophilic proteins exhibit similar structures and dynamics at optimal growth temperatures? A molecular dynamics simulation study

Published in: Journal, Article, Volume : 53, Issue : 2, Pages : 423-434

DOI : 10.1021/ci300474h

Author : Basu, Sohini; Sen, Srikanta

Abstract : Structure and dynamics both are known to be important for the activity of a protein. A fundamental question is whether a thermophilic protein and its mesophilic homolog exhibit similar dynamics at their resp. optimal growth temperatures Here, the authors addressed this question by performing mol. dynamics (MD) simulations of a natural mesophilic-thermophilic homolog pair at their resp. optimal growth temperatures to compare their structural, dynamical, and solvent properties. The proteins chosen were the mesophilic cold-shock protein of Bacillus subtilis and the thermophilic cold-shock protein of B. caldolyticus with resp. optimal growth temperatures at 35.0 and 72.0°. The MD simulations were done in explicit aqueous solvent under periodic boundary and constant pressure and temperature (CPT) conditions and continued for 10.0 ns using the same protocol for the 2 proteins, excepting the temperatures The trajectories were analyzed to compare the properties of the 2 proteins. The results indicated that the dynamical behaviors of the 2 proteins at the resp. optimal growth temperatures were remarkably similar. For the common residues in the thermophilic protein, the rms fluctuations had a general trend to be slightly higher compared to that in the mesophilic counterpart. Lindemann parameter values indicated that only a few residues exhibited solid-like dynamics while the protein as a whole appeared as a molten globule in each case. Interestingly, the water-water interaction was found to be strikingly similar in spite of the difference in temperatures while, the protein-water interaction was significantly different in the 2 simulations.