PARAMETRIZATION, MD SIMULATION, CALCULATION OF POLYALANINE ALPHA-HELIX SPECTRA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The nitroxide spin label 1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl-methanethiosulfonate (MTSSL), commonly used in site-directed spin labeling of proteins, was studied with molecular dynamics (MD) simulations. After developing force field parameters for the nitroxide moiety and the spin label linker, we simulated MTSSL attached to a polyalanine R-helix in explicit solvent to elucidate the factors affecting its conformational dynamics. Electron spin resonance spectra at 9 and 250 GHz were simulated in the time domain using the MD trajectories and including global rotational diffusion appropriate for the tumbling of T4 Lysozyme in solution. Analysis of the MD simulations reveals the presence of significant hydrophobic interactions of the spin label with the alanine side chains