Molecular dynamics simulation of formamide in water using density functional theory and classical potentials

We report the first molecular dynamics simulation of an amide in water in w hich the solute is fully described through quantum mechanics methods (densi ty functional theory in our case). All solute's degrees of freedom are allo wed to vary. The solvent is described through a classical potential. We hav e chosen for our study the simple formamide molecule since it allows hybrid simulations to be carried out at a sophisticated quantum level. More preci sely, we have considered two computational schemes: in the first one, we us e a small double-zeta basis set and a local approximation of the exchange-c orrelation functional whereas, in the second, an extended triple-zeta+polar ization basis set, as well as a gradient-corrected functional, has been emp loyed. The analysis of the results is focused on both structural and energe tic aspects. Particular attention is paid to the time variation of dihedral angles in formamide connected to nitrogen pyramidalization and NH2 subunit rotation. The agreement with available experimental and theoretical data i s satisfactory. Nevertheless, the limits of the method are pointed out, in particular the need to improve the description of the nonelectrostatic term of the solute-solvent interaction potential. One of the main advantages of the hybrid approach is that polarization effects are included in a rigorou s manner. This renders possible a detailed discussion on the role of hydrat ion effects on amides structure, a point of considerable relevance due to t he biochemical importance of the peptidic bond. (C) 1999 American Institute of Physics. [S0021-9606(99)50426-1].