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

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

CHARMM force field parameters for simulation of reactive intermediates in native and thio‐substituted ribozymes

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Poisson–Boltzmann model analysis of binding mRNA cap analogues to the translation initiation factor eIF4E

“…The protein mutants K159A and S209Sp, as well as cap analogue m 7 Gp 4 were modelled using also CHARMM. The model-built fragments were energy minimised using CHARMM, and the CHARMM27 parameters, and force field [28,29]. In all minimisations we used 1000 steps of the Steepest Descents followed by 1000 steps of Adopted Basis Newton-Raphson minimisation algorithms, implemented in CHARMM.…”

Systematic comparison of force fields for microscopic simulations of NaCl in aqueous solutions: Diffusion, free energy of hydration, and structural properties

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