title: Designing "high-affinity, high-specificity" glycosaminoglycan sequences through computerized modeling.
abstract: The prediction of high-affinity and/or high-specificity protein-glycosaminoglycan (GAG) interactions is an inherently difficult task, due to several factors including the shallow nature of the typical GAG-binding site and the inherent size, flexibility, diversity, and polydisperse nature of the GAG molecules. Here, we present a generally applicable methodology termed Combinatorial Library Virtual Screening (CVLS) that can identify potential high-affinity, high-specificity protein-GAG interactions from very large GAG combinatorial libraries and a suitable GAG-binding protein. We describe the CVLS approach along with the rationale behind it and provide validation for the method using the well-known antithrombin-thrombin-heparin system.
authors.affiliation: Department of Medicinal Chemistry, Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh Street, Suite 212, Richmond, VA, 23298, USA.
authors.forename: Nehru Viji
authors.initials: NV
authors.lastname: Sankaranarayanan
authors.forename: Aurijit
authors.initials: A
authors.lastname: Sarkar
authors.forename: Umesh R
authors.initials: UR
authors.lastname: Desai
authors.forename: Philip D
authors.initials: PD
authors.lastname: Mosier
mesh_terms: D000465:Algorithms; D002240:Carbohydrate Sequence; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004187:Disaccharides / Q000737:chemistry; D006025:Glycosaminoglycans / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009005:Monosaccharides / Q000737:chemistry; D015203:Reproducibility of Results
chemical_list: D004187:Disaccharides; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D009005:Monosaccharides