Structure optimization via free energy gradient method: Application to glycine zwitterion in aqueous solution

The free energy gradient method was applied to the multidimensional geometr y optimization of glycine zwitterion (ZW) in aqueous solution in order not only to demonstrate its applicability, but also to examine its efficiency. The method utilizes force on the free energy surface that can be directly c alculated by the molecular dynamics method and the free energy perturbation theory. Then, the most stable ZW structure in aqueous solution was obtaine d within the tolerance assumed, and it was found that the free energy (FE) and enthalpy changes of stabilization from the initial geometry optimized i n the gas phase are -0.9 and -3.5 kcal/mol, respectively, and the amino and carboxyl groups are spatially separated by each other due to their solvati ng with water molecules. Comparing the contributions of enthalpy and entrop y to FE, the former is attributed to the main origin of FE stabilization du ring the optimization procedure, and it was found that solvation entropy pr events water molecules from solvating the ZW more strongly. (C) 2000 Americ an Institute of Physics. [S0021-9606(00)51733-4].