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Multi-state modeling with SAXS profiles

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About MultiFoXS

MultiFoXS is a method for multi-state modeling with SAXS profiles. The method was developed for interpretation of data collected for heterogeneous samples. Many proteins are conformationally heterogeneous in solution. We describe this heterogeneity using multi-state models. A multi-state model is a model that specifies two or more co-existing structural states and values for any other parameter, such as population weights.

The input to MultiFoXS is a protein structure and a SAXS profile. The output is a list of multi-state models that fit best to the input SAXS profile.

Method Overview

The MultiFoXS sever protocol involves three steps [1]:

  1. Conformational sampling. In this step we use Rapidly exploring Random Tree (RRT) search [2,3] to sample the conformational space that is accessible to the input protein. It is recommended to generate ~10,000 conformations.
  2. SAXS scoring. The SAXS profile is calculate for each conformation using FoXS method [4,5].
  3. Multi-state model enumeration. Given ~10,000 input conformations and their computed SAXS profiles, multi-state model enumeration is performed iteratively by branch-and-bound method [6].

References

  1. D. Schneidman-Duhovny, M. Hammel, JA. Tainer, and A. Sali. FoXS, FoXSDock and MultiFoXS: Single-state and multi-state structural modeling of proteins and their complexes based on SAXS profiles. NAR 2016.
  2. NM. Amato, and G. Song. Using motion planning to study protein folding pathways. J Comput Biol. 2002;9(2):149-68.
  3. B Raveh, A Enosh, O Schueler-Furman, and D Halperin. Rapid sampling of molecular motions with prior information constraints. PLoS Comput Biol. 2009 Feb;5(2):e1000295.
  4. D. Schneidman-Duhovny, M. Hammel, and A. Sali. FoXS: A Web server for Rapid Computation and Fitting of SAXS Profiles. NAR 2010.38 Suppl:W540-4.
  5. D. Schneidman-Duhovny, M. Hammel, JA. Tainer, and A. Sali. Accurate SAXS profile computation and its assessment by contrast variation experiments. Biophysical Journal 2013. 105 (4), 962-974
  6. L Carter, SJ Kim, D Schneidman-Duhovny, J Stöhr, G. Poncet-Montange, TM. Weiss, H. Tsuruta, SB. Prusiner, and A. Sali. Prion Protein-Antibody Complexes Characterized by Chromatography-Coupled Small-Angle X-Ray Scattering. Biophys J. 2015 Aug 18;109(4):793-805.

If you use MultiFoXS (version master.f32d80c), please cite:
D. Schneidman-Duhovny, M. Hammel, JA. Tainer, and A. Sali. FoXS, FoXSDock and MultiFoXS: Single-state and multi-state structural modeling of proteins and their complexes based on SAXS profiles. NAR 2016 [ FREE Full Text ]
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