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

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 snap...

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Bibliographic Details
Published in:Biophysical journal 2008-06, Vol.94 (12), p.4924-4931
Main Authors: Kim, Seung Joong, Dumont, Charles, Gruebele, Martin
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Algorithms
APPROXIMATIONS
BASIC BIOLOGICAL SCIENCES
Biophysics
Computation
Computer Simulation
COMPUTERIZED SIMULATION
Crystallography - methods
DYNAMICS
Electromagnetic Fields
INTERACTIONS
Mathematical models
Models, Chemical
Molecular dynamics
MOLECULAR DYNAMICS METHOD
MONTE CARLO METHOD
Monte Carlo methods
Monte Carlo simulation
OPTIMIZATION
POTENTIALS
Protein Binding
Protein Interaction Mapping - methods
PROTEINS
SCATTERING
Scattering, Radiation
Scattering, Small Angle
Spectroscopy, Imaging, Other Techniques
X-rays
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Summary: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.
ISSN:0006-3495
1542-0086
DOI:10.1529/biophysj.107.123240