Extension of the CHARMM general force field to sulfonyl‐containing compounds and its utility in biomolecular simulations

Abstract

Presented is an extension of the CHARMM General Force Field (CGenFF) to enable the modeling of sulfonyl-containing compounds. Model compounds containing chemical moieties such as sulfone, sulfonamide, sulfonate, and sulfamate were used as the basis for the parameter optimization. Targeting high-level quantum mechanical and experimental crystal data, the new parameters were optimized in a hierarchical fashion designed to maintain compatibility with the remainder of the CHARMM additive force field. The optimized parameters satisfactorily reproduced equilibrium geometries, vibrational frequencies, interactions with water, gas phase dipole moments, and dihedral potential energy scans. Validation involved both crystalline and liquid phase calculations showing the newly developed parameters to satisfactorily reproduce experimental unit cell geometries, crystal intramolecular geometries, and pure solvent densities. The force field was subsequently applied to study conformational preference of a sulfonamide based peptide system. Good agreement with experimental IR/NMR data further validated the newly developed CGenFF parameters as a tool to investigate the dynamic behavior of sulfonyl groups in a biological environment. CGenFF now covers sulfonyl group containing moieties allowing for modeling and simulation of sulfonyl-containing compounds in the context of biomolecular systems including compounds of medicinal interest.