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Efficient Ensemble Refinement by Reweighting

preprint
revised on 12.03.2019 and posted on 12.03.2019 by Juergen Koefinger, Lukas S. Stelzl, Klaus Reuter, Cesar Allande, Katrin Reichel, Gerhard Hummer
In integrative structural biology/hybrid modeling approaches, we integrate structural models of macromolecules and experimental data to obtain faithful representations of the structures underlying the data. For example, in ensemble refinement by reweighting we first generate structural ensembles of flexible and dynamic biological macromolecules in molecular simulations. In a subsequent reweighting step, we refine the statistical weights of the structures to strike a balance between the information provided by simulations and by experimental data. For the "Bayesian inference of ensembles" approach (BioEn), we present two complementary methods to solve the underlying challenging high-dimensional optimization problem. We systematically investigate reliability, accuracy, and efficiency of these methods and integrate molecular dynamics simulations of the disordered peptide Ala-5 and NMR J-couplings. We provide an open-source library free of charge at https://github.com/bio-phys/BioEn.

Funding

Max Planck Society

German Research Foundation (CRC902: Molecular Principles of RNA Based Regulation)

History

Email Address of Submitting Author

juergen.koefinger@biophys.mpg.de

Institution

Max Planck Institute of Biophysics

Country

Germany

ORCID For Submitting Author

0000-0001-8367-1077

Declaration of Conflict of Interest

We declare no conflict of interest.

Version Notes

Submitted to JCTC.

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in Journal of Chemical Theory and Computation

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