MOLECULAR MECHANISMS OF PRESSURE-INDUCED CONFORMATIONAL-CHANGES IN BPTI

We have performed a 800 ps molecular dynamics simulation of bovine pan creatic trypsin inhibitor (BPTI) in water coupled to a pressure bath a t 1, 10,000, 15,000, and 20,000 bar. The simulation reproduces quite w ell the experimental behavior of the protein under high pressure, The protein keeps its globular form, but adopts a different conformation w ith a very small reduction in volume. Some residues in the hydrophobic core become exposed to water and a large part of the secondary struct ure of the protein, (60% of the sheet structure and 40% of the helical structure) is denatured between 10 and 15 kbar, This is in good agree ment with experimental data (Goossens, K., et al. fur. J. Biochem, 236 :254-262, 1996) that show denaturation of BPTI between 8 and 14 kbar. A further increase of the pressure results in a freezing of the protei n as deduced from the large decrease of the mobility of the residues. During the simulation, the normal structure of water changes from an i ce Ih-like to an ice VI-like structure, while keeping the liquid state , The driving force of the high pressure induced conformational transi tion seems be the higher compressibility of the water compared with th e protein. This produces a change in the solvent properties and leads to penetration of the solvent into the hydrophobic core. (C) 1996 Wile y-Liss, Inc.