Flexibility and explicit solvent in molecular-dynamics-based docking of protein-glycosaminoglycan systems

Research output: Contribution to journalResearch articleContributedpeer-review



We present Dynamic Molecular Docking (DMD), a novel targeted molecular dynamics-based protocol developed to address ligand and receptor flexibility as well as the inclusion of explicit solvent in local molecular docking. A class of ligands for which docking performance especially benefits from overcoming these challenges is the glycosaminoglycans (GAGs). GAGs are periodic, highly flexible, and negatively charged polysaccharides playing an important role in the extracellular matrix via interaction with proteins such as growth factors and chemokines. The goal of our work has been to develop a proof of concept for an MD-based docking approach and to analyze its applicability for protein-GAG systems. DMD exploits the electrostatics-driven attraction of a ligand to its receptor, treats both as entirely flexible, and considers solvent explicitly. We show that DMD has high predictive significance for systems dominated by electrostatic attraction and demonstrate its capability to reliably identify the receptor residues contributing most to binding.


Original languageEnglish
Pages (from-to)582-592
Number of pages11
JournalACS: Journal of Chemical Information and Modeling
Issue number2
Publication statusPublished - 24 Feb 2014

External IDs

Scopus 84894667941



  • Glycosaminoglycans/metabolism, Ligands, Molecular Docking Simulation, Molecular Dynamics Simulation, Protein Conformation, Proteins/chemistry, Solvents/chemistry, Static Electricity, Thermodynamics