ORIGINAL PAPER A coupled two-dimensional main chain torsional potential

Abstract Main chain torsions of alanine dipeptide are pa-rameterized into coupled 2-dimensional Fourier expansions based on quantum mechanical (QM) calculations at M06 2X/aug-cc-pvtz//HF/6-31G* * level. Solvation effect is con-sidered by employing polarizable continuum model. Utilization of the M06 2X functional leads to precise potential energy surface that is comparable to or even better than MP2 level, but with much less computational demand. Parameterization of the 2D expansions is against the full main chain torsion space instead of just a few low energy conforma-tions. This procedure is similar to that for the development of AMBER03 force field, except unique weighting factor was assigned to all the grid points. To avoid inconsistency between quantum mechanical calculations and molecular modeling, the model peptide is further optimized at molecular mechanics level with main chain dihedral angles fixed before the calcula-tion of the conformational energy on molecular mechanical level at each grid point, during which generalized Born model is employed. Difference in solvation models at quantum me-chanics and molecular mechanics levels makes this parameter-ization procedure less straightforward. All force field parameters other than main chain torsions are taken from existing AMBER force field. With this new main chain torsion terms, we have studied the main chain dihedral distributions of ALA dipeptide and pentapeptide in aqueous solution. The re-sults demonstrate that 2D main chain torsion is effective in delineating the energy variation associated with rotations along main chain dihedrals. This work is an implication for the necessity of more accurate description of main chain torsions in the future development of ab initio force field and it also raises a challenge to the development of quantum mechanical methods, especially the quantum mechanical solvation models