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

TLDR

Empirical force‑field calculations on biological molecules provide atomic detail linking structure to function, but their accuracy depends on force‑field quality. This manuscript optimizes the CHARMM27 all‑atom force field for nucleic acids and presents the resulting parameters. The optimization uses an iterative approach that reproduces small‑molecule experimental and quantum‑mechanical data and condensed‑phase DNA/RNA structural properties, prioritizing macromolecular targets while maintaining small‑molecule agreement. The new parameters advance the CHARMM all‑atom biomolecular force field for proteins, lipids, and nucleic acids. © 2000 John Wiley & Sons, Inc., J Comput Chem 21:86–104.

Abstract

Empirical force-field calculations on biological molecules represent an effective method to obtain atomic detail information on the relationship of their structure to their function. Results from those calculations depend on the quality of the force field. In this manuscript, optimization of the CHARMM27 all-atom empirical force field for nucleic acids is presented together with the resulting parameters. The optimization procedure is based on the reproduction of small molecule target data from both experimental and quantum 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 different contributions from the individual moieties in the nucleic acids are properly balanced to yield condensed phase properties of DNA and RNA, which are consistent with experiment. The quality of the presented force field in reproducing 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 continued development of the CHARMM all-atom biomolecular force field for proteins, lipids, and nucleic acids. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 86–104, 2000