SAXS-Guided Metadynamics

D Kimanius and I Pettersson and G Schluckebier and E Lindahl and M Andersson, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 11, 3491-3498 (2015).

DOI: 10.1021/acs.jctc.5b00299

The small-angle X-ray scattering (SAXS) methodology enables structural characterization of biological macromolecules in solution. However, because SAXS provides low-dimensional information, several potential structural configurations can reproduce the experimental scattering profile, which severely complicates the structural refinement process. Here, we present a bias-exchange metadynamics refinement protocol that incorporates SAXS data as collective variables and therefore tags all possible configurations with their corresponding free energies, which allows identification of a unique structural solution. The method has been implemented in PLUMED and combined with the GROMACS simulation package, and as a proof of principle, we explore the Trp-cage protein folding landscape.

Return to Publications page