Explicit solvent repulsive scaling replica exchange molecular dynamics (RS-REMD) in molecular modeling of protein-glycosaminoglycan complexes.

Autor: Marcisz M; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.; Intercollegiate Faculty of Biotechnology, Universuty of Gdańsk and Medical University of Gdańsk, Gdańsk, Poland., Gaardløs M; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland., Bojarski KK; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.; Department of Physical Chemistry, Gdańsk University of Technology, Gdańsk, Poland., Siebenmorgen T; Institute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany., Zacharias M; Physics Department, Technical University of Munich, Garching, Germany., Samsonov SA; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Jazyk: angličtina
Zdroj: Journal of computational chemistry [J Comput Chem] 2022 Sep 15; Vol. 43 (24), pp. 1633-1640. Date of Electronic Publication: 2022 Jul 07.
DOI: 10.1002/jcc.26965
Abstrakt: Glycosaminoglcyans (GAGs), linear anionic periodic polysaccharides, are crucial for many biologically relevant functions in the extracellular matrix. By interacting with proteins GAGs mediate processes such as cancer development, cell proliferation and the onset of neurodegenerative diseases. Despite this eminent importance of GAGs, they still represent a limited focus for the computational community in comparison to other classes of biomolecules. Therefore, there is a lack of modeling tools designed specifically for docking GAGs. One has to rely on existing docking software developed mostly for small drug molecules substantially differing from GAGs in their basic physico-chemical properties. In this study, we present an updated protocol for docking GAGs based on the Repulsive Scaling Replica Exchange Molecular Dynamics (RS-REMD) that includes explicit solvent description. The use of this water model improved docking performance both in terms of its accuracy and speed. This method represents a significant computational progress in GAG-related research.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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