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Designing “High-Affinity, High-Specificity” Glycosaminoglycan Sequences Through Computerized Modeling

  • Nehru Viji Sankaranarayanan
  • Aurijit Sarkar
  • Umesh R. Desai
  • Philip D. MosierEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1229)

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.

Key words

Glycosaminoglycan (GAG) Docking Virtual library Virtual screening (VS) Genetic algorithm (GA) Molecular interaction Specificity 

Notes

Acknowledgements

This work was supported by the grants HL090586 and HL107152 from the National Institutes of Health and by Award Number S10RR027411 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Nehru Viji Sankaranarayanan
    • 1
  • Aurijit Sarkar
    • 1
  • Umesh R. Desai
    • 1
  • Philip D. Mosier
    • 1
    Email author
  1. 1.Department of Medicinal Chemistry, Institute for Structural Biology and Drug DiscoveryVirginia Commonwealth UniversityRichmondUSA

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