Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
A full exploration of the conformational ensembles of nucleic acid structural motifs
Ensembles of optimized molecular dynamics simulations engines on CPUs and GPUs, coupled with access to large-scale computational resources available through Blue Waters and XSEDE, have enabled the community to reproducibly and fully explore the conformational ensembles of nucleic acid structural motifs. This has allowed the community to better validate and assess currently available force fields for nucleic acids. The results clearly demonstrate that when sampling near experimental structures, the simulations are able to well reproduce and augment structure and dynamic information inferred from experiment. Yet, when pushed further, most of the force fields tend to break down. This ability to fully explore the accessible space provides an opportunity to better scale the force field space and to suggest means to improve the underlying representation. This brief talk will highlight our experiences with RNA tetranucleotides and tetraloops, comparing and contrasting the results with different force fields, how well the simulation results reproduce experiment, and highlight potential paths towards even more reliable simulation of nucleic acid structure.
Computer time is acknowledged from NSF XSEDE Allocation MCA01S027, XSEDE/GeorgiaTech KIDS and Keeneland systems, NSF/NCSA/U Illinois Blue Waters Petascale Resource (PRAC OCI-1036208, OCI 0725070, and ACI-1238993), Anton computer time was provided by the National Center for Multiscale Modeling of Biological Systems (MMBioS, P41GM103712-S1) from the NIH and the Pittsburgh Supercomputing Center (PSC12038P, PSCA00033P). The Anton machine at PSC was generously made available by D. E. Shaw Research.
Thomas Cheatham III
Department of Medicinal Chemistry