Docking glycosaminoglycans to proteins: analysis of solvent inclusion

• DOI: 10.1007/s10822-011-9433-1
• Publication Date: 2011-05-19T08:57:56Z
• Authors: Sergey A. Samsonov; Joan Teyra; M. Teresa Pisabarro
• Keywords: Docking (animal)

Glycosaminoglycans (GAGs) are anionic polysaccharides, which participate in key processes the extracellular matrix by interactions with protein targets. Due to their charged nature, accurate consideration of electrostatic and water-mediated is indispensable for understanding GAGs binding properties. However, solvent often overlooked molecular recognition studies. Here we analyze abundance GAG-protein interfaces investigate challenges adding explicit docking experiments. We observe PDB being significantly more hydrated than protein–protein interfaces. Furthermore, applying dynamics approaches estimate that about half water-mediated. With a dataset eleven complexes how inclusion affects Autodock 3, eHiTs, MOE FlexX docking. develop an approach de novo place into site prior docking, uses GRID program predict positions waters locate possible areas displacement upon ligand binding. To placement performance, compare these results those obtained taking account information position crystal structure. In general, improves methods. Our data show 3 performs best, though it experiences difficulties quantitatively reproduce experimental on specificity heparin/heparan sulfate disaccharides IL-8. work highlights current introducing protein-GAGs studies, crucial exploiting full potential molecules rational engineering.