Molecular dynamics simulation unrestrained

Moving beyond standard DNA and RNA duplexes, simulations of chemically modified DNA provide a further test of the simulation methods. To this end, we performed unrestrained molecular dynamics simulations on a standard d(CGCGAATTCGCG)2 dodecamer duplex in aqueous solution and its phosphoramidate (N3 -P) analog using the particle mesh Ewald summation technique (5) and recent AMBER force field (10). In the modified dodecamer each phosphodiester has been replaced by a phosphoramidate unit with a N3-P5 intemucleoside linkage. 

Simulations of an RNA hairpin loop showed that its structure was tremendously stable on a nanosecond time scale (13) and simulations of a RNA duplex showed that in addition to A-RNA, B-RNA is also stable on a nanosecond time scale (31). This brings up the issue of conformational sampling in simulations of RNA with the Cornell et al. force field which has been extensively studied in our lab. At the meeting, we presented the results of five unrestrained molecular dynamics simulations of an RNA tetraloop, describing our efforts to observe the conversion between an... 

The system was equilibrated for more than 100 ps the equilibration was checked by monitoring energy trajectories and root mean square (rms) deviations from the X-ray structure. Using 8 parallel processors, it took 1 hour to calculate a 2 ps simulation. The restraints on the system during the molecular dynamics calculation were released in a stepwise mode, first on side chains and then on other atoms. The rms deviation of all Ca atoms between the cytochrome b subimit in the X-ray structure and the unrestrained model after 120 ps was 1.38 A. 

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