Evaluation of replica exchange with repulsive scaling approach for docking glycosaminoglycans.

Maszota-Zieleniak, Martyna; Marcisz, Mateusz; Kogut, Małgorzata M; Siebenmorgen, Till; Zacharias, Martin; Samsonov, Sergey A

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.