title: Base Flipping in a GCGC Containing DNA Dodecamer:  A Comparative Study of the Performance of the Nucleic Acid Force Fields, CHARMM, AMBER, and BMS.
abstract: The improving quality of empirical force field parameters along with other methodological improvements and ever increasing computational resources have lead to more reliable computations on biological macromolecules. In the case of oligonucleotides, three force fields, namely CHARMM27, AMBER4.1, and BMS, have been developed and are widely used by the simulation community. Testing of these force fields to date has primarily focused on their treatment of the canonical forms of DNA and RNA. However, many biological functions of oligonucleotides involve significant variation of their structures from the canonical forms. In the present work, the three force fields are evaluated via computation of potentials of mean force (PMF) of the base flipping process in a DNA dodecamer, 5'-GTCAGCGCATGG-3'. Results are compared with available experimental data on the equilibrium between the opened and closed (i.e. Watson-Crick base paired) state of the underlined C and its WC partner G. Quantitative analysis shows CHARMM to be in the best agreement with experiment, closely followed by AMBER with BMS in the poorest agreement. Various components contributing to the change in the free energy such as base pair interactions, stacking interactions, solvation effects, and intrinsic potential energy changes were evaluated and compared. The results indicate that while all three force fields reasonably represent the canonical structures, the balance of forces contributing to their structural and dynamic properties differ significantly.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201.
authors.forename: U Deva
authors.initials: UD
authors.lastname: Priyakumar
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell