A new spectroscopic molecular mechanics force field. Parameters for proteins

We present the development of a new spectroscopic molecular mechanics potential for proteins. SPASIBA merges the torsional, van der Waals, electrostatic, and hydrogen bond potentials of AMBER with the Urey–Bradley–Shimanouchi terms for bond lengths and bond angles. To begin, SPASIBA was consistently parametrized to structural, energies, and vibrational frequency data of model compounds representative of the 16 nonaromatic acids: n‐alkanes, alcohols, acids, ethyl methyl sulfide, methyl sulfide in water, ethanethiol, dimethyl disulfide, guanidium ion, propionamide, N‐methylacetamide, N‐methylisobutyramide, and N‐isopropylacetamide. The parameters were then transferred to N‐acetyl‐X methylamides (where X=Gly, L‐Ala, L‐Pro), the L‐Leu, L‐Cys, and L‐Thr amino acids blocked by the carboxylate and ammonium ions, and the right‐handed deca‐alanine and Gly‐L‐Pro‐Gly‐Gly peptides. Results show that SPASIBA reproduces vibrational frequencies (with much higher accuracy than present molecular mechanics potentials), as well as potential energy distributions of normal modes. For the 532 fundamental frequencies considered for refining the force field, the mean frequency error is 13 cm⁻¹. This force field, which can be incorporated in molecular dynamics simulations, is also found to provide useful insights into the conformation/vibrational spectrum relationships. This ability is illustrated on the Gly and L‐Ala dipeptides, as well as the polypeptides.