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Jan-Philip Gehrcke, Sergey A. Samsonov, M. Teresa Pisabarro
Molecular docking is the computational method used for predicting binding conformations for a given pair of receptor and ligand. For the sake of computational feasibility, a common approximation in docking approaches, among others, is to restrict the conformational flexibility of both ligand and receptor and to disregard the explicit impact of solvent molecules on intermolecular interactions. In view of the ever-increasing computing power, we have implemented a docking protocol based on the steered molecular dynamics (SMD) approach using the AMBER suite. There, we treat the molecular system as entirely flexible with molecular interactions described by well-established force fields. Additionally, in contrast to common docking approaches, the effect of solvent on receptor-ligand binding is directly accounted for due to the presence of explicit solvent molecules. As a test case for this method, we use a set of protein-glycosaminoglycan (GAG) complexes from the PDB. Docking GAGs is especially challenging: besides being long and highly flexible, these linear polysaccharides are strongly negatively charged, which is why water molecules play a crucial role in GAG recognition processes. Here, we present the methodology and an analysis of its performance regarding GAG-protein complexes in comparison to classical docking methods. |
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