Electrostatic effects on the alpha-helix and beta-strand formation of BPTI(16-36) studied by Monte Carlo simulated annealing.

The electrostatic effects on the secondary structure forming tendencies of a peptide fragment with residues 16-36 of bovine pancreatic trypsin inhibitor, BPTI(16-36), are studied using Monte Carlo simulated annealing simulations. We consider three dielectric functions epsilon(r) of distance r: constant dielectric function (epsilon = 2; strong electrostatic interactions) and sigmoidal functions varying from epsilon(0) = 2 to epsilon(infinity) = 47 (intermediate) and to epsilon(infinity) = 78 (weak). Simulations with epsilon = 2 suggest that this peptide exhibits a significant propensity for beta-strand formations in accordance with a beta-sheet structure of the relevant segment in native BPTI. The tendency for alpha-helix formations becomes almost comparable with that of beta-strands in the simulation with epsilon(infinity) = 47, and there appears no appreciable conformational propensity for this case. Finally, the results with epsilon(infinity) = 78 generate low-energy conformations with conspicuous alpha-helices. These findings suggest the possibility that the change in electrostatic interactions can be the key factor for the conformational transitions of peptides between alpha-helix and beta-sheet that have recently been observed in experiments. These changes in electrostatic interactions can arise from those in various environmental factors such as conformations of the rest of the protein molecule and solvent conditions.