Work

Estimating glycosaminoglycan–protein interaction affinity: water dominates the specific antithrombin–heparin interaction

Year: 2016

Type: article

Abstract: Glycosaminoglycan (GAG)-protein interactions modulate many important biological processes. Structure-function studies on GAGs may reveal probes and drugs, but their structural complexity and highly acidic nature confound such work. Productivity will increase if we are able to identify tight-binding oligosaccharides in silico. An extension of the CHARMM force field is presented to enable modeling of polysaccharides containing sulfamate functionality, and is used to develop a reliable alchemical free-energy perturbation protocol that estimates changes in affinity for the prototypical heparin-antithrombin system to within 2.3 kcal/mol using modest simulation times. Inclusion of water is crucial during simulation as solvation energy was equal in magnitude to the sum of all other thermodynamic factors. In summary, we have identified and optimized a reliable method for estimation of GAG-protein binding affinity, and shown that solvation is a crucial component in GAG-protein interactions.

Source: Glycobiology

DOI: 10.1093/glycob/cww073

Authors: Aurijit Sarkar, Wenbo Yu, Umesh R Desai, Alexander D MacKerell, Philip D Mosier

Institutions: High Point University, Virginia Commonwealth University, University of Maryland, Baltimore

Language: English

Topic: Proteoglycans and glycosaminoglycans research

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: bronze