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Simulation-Based Fitting of Protein-Protein Interaction Potentials to SAXS Experiments

Seung Joong Kim ^*, Charles Dumont ^* and Martin Gruebele ^* 

^* Department of Physics, and Center for Biophysics and Computational Biology and Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois

Correspondence: Address reprint requests to Martin Gruebele, Dept. of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801. Tel.: 217-333-1624; E-mail: gruebele{at}scs.uiuc.edu.

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.