title: Simulation-based fitting of protein-protein interaction potentials to SAXS experiments.
abstract: We present a new method for computing interaction potentials of solvated proteins directly from small-angle x-ray scattering data. An ensemble of proteins is modeled by Monte Carlo or molecular dynamics simulation. The global x-ray scattering of the whole model ensemble is then computed at each snapshot of the simulation, and averaged to obtain the x-ray scattering intensity. Finally, the interaction potential parameters are adjusted by an optimization algorithm, and the procedure is iterated until the best agreement between simulation and experiment is obtained. This new approach obviates the need for approximations that must be made in simplified analytical models. We apply the method to lambda repressor fragment 6-85 and fyn-SH3. With the increased availability of fast computer clusters, Monte Carlo and molecular dynamics analysis using residue-level or even atomistic potentials may soon become feasible.
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Seung Joong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Charles
authors.initials: C
authors.lastname: Dumont
authors.forename: Martin
authors.initials: M
authors.lastname: Gruebele
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D003461:Crystallography / Q000379:methods*; D004574:Electromagnetic Fields; D008956:Models, Chemical; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D012542:Scattering, Radiation; D053838:Scattering, Small Angle