title: Restrained-ensemble molecular dynamics simulations based on distance histograms from double electron-electron resonance spectroscopy.
abstract: DEER (double electron-electron resonance) spectroscopy is a powerful pulsed ESR (electron spin resonance) technique allowing the determination of spin-spin distance histograms between site-directed nitroxide label sites on a protein in their native environment. However, incorporating ESR/DEER data in structural refinement is challenging because the information from the large number of distance histograms is complex and highly coupled. Here, a novel restrained-ensemble molecular dynamics simulation method is developed to incorporate the information from multiple ESR/DEER distance histograms simultaneously. Illustrative tests on three coupled spin-labels inserted in T4 lysozyme show that the method efficiently imposes the experimental distance distribution in this system. Different rotameric states of the χ1 and χ2 dihedrals in the spin-labels are also explored by restrained ensemble simulations. Using this method, it is hoped that experimental restraints from ESR/DEER experiments can be used to refine structural properties of biological systems.
authors.affiliation: Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, University of Chicago, Chicago, Illinois 60637, United States. roux@uchicago.edu
authors.forename: Benoît
authors.initials: B
authors.lastname: Roux
authors.forename: Shahidul M
authors.initials: SM
authors.lastname: Islam
mesh_terms: D017122:Bacteriophage T4 / Q000201:enzymology; D003497:Cyclic N-Oxides / Q000737:chemistry; D004578:Electron Spin Resonance Spectroscopy; D004583:Electrons; D008698:Mesylates / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D008698:Mesylates; D013113:Spin Labels; C034248:(1-oxyl-2,2,5,5-tetramethylpyrroline-3-methyl)methanethiosulfonate; D009113:Muramidase