All-atom empirical force field for nucleic acids: I. Parameter optimization based on small molecule and condensed phase macromolecular target data

Empirical force-field calculations on biological molecules represent an eff ective method to obtain atomic detail information on the relationship of th eir structure to their function. Results from those calculations depend on the quality of the force field. In this manuscript, optimization of the CHA RMM27 all-atom empirical force field for nucleic acids is presented togethe r with the resulting parameters. The optimization procedure is based on the reproduction of small molecule target data from both experimental and quan tum mechanical studies and condensed phase structural properties of DNA and RNA. Via an iterative approach, the parameters were primarily optimized to reproduce macromolecular target data while maximizing agreement with small molecule target data. This approach is expected to ensure that the differe nt contributions from the individual moieties in the nucleic acids are prop erly balanced to yield condensed phase properties of DNA and RNA, which are consistent with experiment. The quality of the presented force field in re producing both crystal and solution properties are detailed in the present and an accompanying manuscript (MacKerell and Banavali, J Comput Chem, this issue). The resultant parameters represent the latest step in the continue d development of the CHARMM all-atom biomolecular force field for proteins, lipids, and nucleic acids. (C) 2000 John Wiley & Sons, Inc.