Please use this identifier to cite or link to this item: doi:10.22028/D291-28925
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Title: SAXS-Restrained Ensemble Simulations of Intrinsically Disordered Proteins with Commitment to the Principle of Maximum Entropy
Author(s): Hermann, Markus R.
Hub, Jochen Sebastian
Language: English
Title: Journal of chemical theory and computation
Volume: 15
Issue: 9
Startpage: 5103
Endpage: 5115
Publisher/Platform: American Chemical Society (ACS)
Year of Publication: 2019
Publikation type: Journal Article
Abstract: Intrinsically disordered proteins (IDPs) play key roles in biology and disease, rationalizing the wide interest in deriving accurate solution ensembles of IDPs. Molecular dynamics (MD) simulations of IDPs often suffer from force-field inaccuracies, suggesting that simulations must be complemented by experimental data to obtain physically correct ensembles. We present a method for integrating small-angle X-ray scattering (SAXS) data on-the-fly into MD simulations of disordered systems, with the aim to bias the conformational sampling toward agreement with ensemble-averaged SAXS data. By coupling a set of parallel replicas to the data and following the principle of maximum entropy, this method applies only a minimal bias. Using the RS peptide as a test case, we analyze the influence of (i) the number of parallel replicas, (ii) the scaling of the force constant for the SAXS-derived biasing energy with the number of parallel replicas, and (iii) the force field. The refined ensembles are cross-validated against experimental 3JHN-Hα couplings and further compared in terms of Cα distance maps and secondary structure content. Remarkably, we find that the applied force field only has a small influence on the SAXS-refined ensemble, suggesting that incorporating SAXS data into MD simulations may greatly reduce the force-field bias.
DOI of the first publication: 10.1021/acs.jctc.9b00338
Link to this record: hdl:20.500.11880/27780
ISSN: 1549-9618
Date of registration: 14-Sep-2019
Faculty: NT - Naturwissenschaftlich- Technische Fakultät
Department: NT - Physik
Professorship: NT - Prof. Dr. Jochen Hub
Collections:Die Universitätsbibliographie

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