Testing and Optimizing the Drude Polarizable Force Field for Blocked Amino Acids Based on High-Level Quantum-Mechanical Energy Surfaces

The CHARMM Drude polarizable force field was tested based on high-level quantum-mechanical calculations using all low lying energy minima occurring in all 15 neutral blocked amino acids. Several bonded terms were reparameterized to improve the agreement between the two energy surfaces. The correct reproduction of conformational substates of amino acids was tested for the CHARMM Drude polarizable force field. This was achieved by evaluating the reorganization energies for all low lying energy minima occurring in all 15 neutral blocked amino acids on a quantum-mechanical (QM) energy surface at the MP2/cc-pVDZ level. The results indicate that the bonded parameters of the N-acetyl (ACE) and N-Methylamide (CT3) blocking groups lead to significant discrepancies. A reparametrization of five bond angles significantly improved the agreement with the QM energy surface. The corrected Drude force field exhibits almost the same average reorganization energies relative to the MP2 energy surface as the AM1 and PM3 semi-empirical methods.