SUNY at Albany
June 19-23, 2001
Molecular dynamics simulations of nucleic acids: Issues with nanosecond length simulation, salt, solvation, energetics and treatment of the electrostatics.
Thanks to advances in empirical force fields, computer power, and the development of faster methods for handling solvation and electrostatic interactions, bio-molecular simulation has seen tremendous advance. This includes not only accurately representing subtle sequence specific structure in nucleic acid duplexes, but the observation of spontaneous conformational transitions due to changes in the environment, consistent with experiment. However, to move beyond once off demonstrations of the reliability of the simulation protocol it is necessary and desirable to continually probe the sensitivity of the methods. This involves comparison of simulation protocols and empirical force fields for nucleic acids to better understand the potential artifacts. Artifacts that may creep into the simulations and bias the results may result from incomplete treatment of solvation or salt effects, the induction of artificial periodicity and the short time scale of the simulations, among other issues. Here we revisit some of our earlier investigations (1) with longer simulations and more detailed analysis to better probe finite size and finite time scale artifacts and potential artifacts due to incomplete solvation or minimal salt.Reference and Footnotes (1) T. E. Cheatham, III and P. A. Kollman "Molecular dynamics simulation of nucleic acids in solution: How sensitive are the results to small perturbations in the force field and environment?" in Structure, Motion, Interaction and Expression of Biological Macromolecules, Proceedings of the Tenth Conversation, State University of New York, Albany NY, Adenine Press) p. 99-116 (1998).
Thomas E. Cheatham, III,
Department of Medicinal Chemistry
2000 East, 30 South, Skaggs Hall Room 201
Salt Lake City, UT 84112-5820