Monte Carlo simulation study of thermal fluctuations and conformational energy surface of a small protein, basic pancreatic trypsin inhibitor

The conformational energy surface of a small protein, basic pancreatic trypsin inhibitor, is studied to characterize small-amplitude thermal fluctuations in the protein molecule. In order to see the shape of the conformational energy surface near the energy minimum point, the thermal equilibrium of the molecule is simulated by the Monte Carlo method of Metropolis et al. From the sample of the equilibrium population, which reflects the shape of the energy surface, orthogonal directions are generated in the conformational space, and the conformational energy is actually calculated along these directions. All energy profiles along these directions are found to be approximately a parabola within the range of thermal fluctuations, which suggests the possibility of harmonic approximation to the conformational energy surface of the globular protein.