MOLECULAR-DYNAMICS SIMULATIONS IN AQUEOUS-SOLUTION - APPLICATION TO FREE-ENERGY CALCULATION OF OLIGOPEPTIDES

We developed a new method to calculate thermodynamic parameters with t he Poisson-Boltzmann equation (PBEQ) and molecular dynamics (MD) calcu lations. This method treats the solvent effect on the solute conformat ion as a potential of mean force (PMF), so no explicit water is requir ed in the calculation. The usage of the PBEQ enables the reduction of conformational space to be explored, and we used it to calculate the c onformational free energy of alanine dipeptide and hydrogen bond formi ng-deforming (helix-coil) transition free energy of oligopeptides Ace- Ala(3)-NMe in aqueous solution. We found that (i) the conformational f ree energy of alanine dipeptide agrees with previous works, (ii) the h ydrogen bond forming-deforming transition free energy G(helix) - G(coi l) was 1.27 +/- 0.27 kcal/mol, and this deviation was small in compari son with the explicit water calculation, (iii) the solvent effect stab ilized the hydrogen bond forming conformation, and (iv) electrostatic dipole moment and accessible surface area of polar atoms have an impor tant role for the hydrogen bond forming-deforming transition free ener gy.