Datensatz

Zusammenfassung

Nucleic acid force fields have been shown to reproduce structural properties of DNA and RNA very well, but comparative studies with respect to thermodynamic properties are rare. As a test for thermodynamic properties, we have computed hydration free energies and chloroform-to-water partition coefficients of nucleobases using the AMBER-99, AMBER-gaff, CHARMM-27, GROMOS-45a4/53a6 and OPLS-AA force fields. A mutual force field comparison showed a very large spread in the calculated thermodynamic properties, demonstrating that some of the parameter sets require further optimization. The choice of solvent model used in the simulation does not have a significant effect on the results. Comparing the hydration free energies obtained by the various force fields to the adenine and thymine experimental values showed a very large deviation for the GROMOS and AMBER parameter sets. Validation against experimental partition coefficients showed good agreement for the CHARMM-27 parameter set. In view of mutation studies, differences in partition coefficient between two bases were also compared, and good agreement between experiments and calculations was found for the AMBER-99 parameter set. Overall, the CHARMM-27 parameter set performs best with respect to the thermodynamic properties tested here. © 2012 Wiley Periodicals, Inc.