Temperature and pressure dependence of alanine dipeptide studied by multibaric-multithermal molecular dynamics simulations

We applied the multibaric-multimermal (MUBATH) molecular dynamics (MD) algorithm to an alanine dipeptide in explicit water. The MUBATH MD simulation covered a wide range of conformational space and sampled the states of Pu, C, α, α, α, and C. On the outer hand, the conventional isobaric-isothermal simulation was trapped in local-minimum free-energy states and sampled only a few of them. We calculated the partial molar enthalpy difference AH and partial molar volume difference ΔV among these states by the MUBATH simulation using the AMBER parm99 and AMBER parm96 force fields and two sets of initial conditions. We compared these results with mose from Raman spectroscopy experiments. The Raman spectroscopy data of ΔH for the C state against the P state agreed with both MUBATH data with the AMBER parm96 and parm99 force fields. The partial molar enthalpy difference AH for the α state and the partial molar volume difference Δ for the C state by the Raman spectroscopy agreed with those for the AMBER parm96 force field. On the other hand, ΔV for the αR state by the Raman spectroscopy was consistent with our AMBER-parm99 force-field result. All the experimental results fall between those of simulations using AMBER parm96 and parm99 force fields, suggesting that the ideal force-field parameters lie between those of AMBER parm96 and parm99. © 2008 American Chemical Society.