Reverse Mapping of Coarse Grained Polyglutamine Conformations from PRIME20 Sampling.

Autor: Kunze T; Faculty of Natural Sciences II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120, Halle, Germany., Dreßler C; Institut für Physik, Ilmenau University of Technology, Weimarer Straße 32, 98693, Ilmenau, Germany., Lauer C; Faculty of Natural Sciences II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120, Halle, Germany., Paul W; Faculty of Natural Sciences II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120, Halle, Germany., Sebastiani D; Faculty of Natural Sciences II, Martin-Luther University Halle-Wittenberg, Von-Danckelmann-Platz 4, 06120, Halle, Germany.
Jazyk: angličtina
Zdroj: Chemphyschem : a European journal of chemical physics and physical chemistry [Chemphyschem] 2024 May 02; Vol. 25 (9), pp. e202300521. Date of Electronic Publication: 2024 Mar 28.
DOI: 10.1002/cphc.202300521
Abstrakt: An inverse coarse-graining protocol is presented for generating and validating atomistic structures of large (bio-) molecules from conformations obtained via a coarse-grained sampling method. Specifically, the protocol is implemented and tested based on the (coarse-grained) PRIME20 protein model (P20/SAMC), and the resulting all-atom conformations are simulated using conventional biomolecular force fields. The phase space sampling at the coarse-grained level is performed with a stochastical approximation Monte Carlo approach. The method is applied to a series of polypeptides, specifically dimers of polyglutamine with varying chain length in aqueous solution. The majority (>70 %) of the conformations obtained from the coarse-grained peptide model can successfully be mapped back to atomistic structures that remain conformationally stable during 10 ns of molecular dynamics simulations. This work can be seen as the first step towards the overarching goal of improving our understanding of protein aggregation phenomena through simulation methods.
(© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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