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

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

SUBMITTER: Sarkar A 

PROVIDER: S-EPMC5072149 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature