LONG TIME DYNAMICS OF BIOMOLECULES: COMPARISON OF MOLECULAR DYNAMICS & ESR

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Molecular dynamics (MD) simulations of biological molecules add considerably to our understanding of their function. Nevertheless, a significant drawback is in their time scales. Even with the rapid growth in computer power, most simulations are still limited to a few nanoseconds of real time. This time domain is far too short to study many biophysical processes, such as conformational transitions in proteins, and protein folding. Elber has been developing an alternative approach to explore significantly more extended time scales. The alternative approach maintains the advantages of MD an atomically detailed picture, and wide applicability. EPR experiments enrich our understanding of protein dynamics. They provide detailed information on the motions of probe groups on a wide range of time scales. Ideally, one would like to compute ESR spectra directly from MD simulations. The orientation dynamics of the spin is coupled to molecular motions and makes it possible to probe specific macromolecular motions. The motions can be extracted from straightforward MD simulations. We also plan to perform intermediate computations in which information from MD simulations will enrich the phenomenological theories. We are investigating the protein lysozyme. In our MD studies we model the spin label MTSSL that binds to cysteine residues. The MD trajectories are about five to ten nanoseconds. The simulations include explicit water solvation and summation of long-range electrostatic interactions. The orientation of the nitroxide spin label with respect to the magnetic field have been computed from the simulation using time averages and averages over different trajectories. The results are yielding the motions important to reproduce the spectra. A first psper on this has been published in J. Phys