Maszota-Zieleniak Martyna, Marcisz Mateusz, Kogut Małgorzata M, Siebenmorgen Till, Zacharias Martin, Samsonov Sergey A
Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Physics Department, Technical University of Munich, Garching, Germany.
J Comput Chem. 2021 Jun 5;42(15):1040-1053. doi: 10.1002/jcc.26496. Epub 2021 Mar 25.
Glycosaminoglycans (GAGs), long linear periodic anionic polysaccharides, are key molecules in the extracellular matrix (ECM). Therefore, deciphering their role in the biologically relevant context is important for fundamental understanding of the processes ongoing in ECM and for establishing new strategies in the regenerative medicine. Although GAGs represent a number of computational challenges, molecular docking is a powerful tool for analysis of their interactions. Despite the recent development of GAG-specific docking approaches, there is plenty of room for improvement. Here, replica exchange molecular dynamics with repulsive scaling (REMD-RS) recently proved to be a successful approach for protein-protein complexes, was applied to dock GAGs. In this method, effective pairwise radii are increased in different Hamiltonian replicas. REMD-RS is shown to be an attractive alternative to classical docking approaches for GAGs. This work contributes to setting up of GAG-specific computational protocols and provides new insights into the nature of these biological systems.
糖胺聚糖（GAGs）是长链线性周期性阴离子多糖，是细胞外基质（ECM）中的关键分子。因此，在生物学相关背景下解读它们的作用，对于从根本上理解ECM中正在进行的过程以及建立再生医学的新策略至关重要。尽管GAGs带来了许多计算挑战，但分子对接是分析它们相互作用的强大工具。尽管最近开发了针对GAGs的对接方法，但仍有很大的改进空间。在这里，最近被证明对蛋白质-蛋白质复合物是一种成功方法的带排斥缩放的复制交换分子动力学（REMD-RS）被应用于对接GAGs。在这种方法中，有效成对半径在不同的哈密顿复制品中增加。REMD-RS被证明是一种比传统对接方法更具吸引力的GAGs对接替代方法。这项工作有助于建立针对GAGs的计算协议，并为这些生物系统的性质提供新的见解。
