Search
Close this search box.

Prediction of Heparin Oligosaccharide Binding Geometries onto Proteins

Author(s)

SG. Holmes & UR. Desai

Sources

Biomolecules 2023, 13, 1633. https://doi.org/10.3390/biom13111633

Assessing Genetic Algorithm-Based Docking Protocols

Although molecular docking has evolved dramatically over the years, its application to glycosaminoglycans (GAGs) has remained challenging because of their intrinsic flexibility, highly anionic character and somewhat ill-defined binding site on proteins. GAGs have been treated as either fully “rigid” or fully “flexible” in molecular docking.  The authors reasoned that an intermediate semirigid docking (SRD) protocol might better recapitulate native heparin/heparan sulfate (Hp/HS) topologies. They investigate 18 Hp/HS–protein co-complexes containing chains from disaccharide to decasaccharide using genetic algorithm-based docking with rigid, semi-rigid, and flexible docking protocols.

Their work reveals that rigid and semi-rigid protocols recapitulate native poses for longer chains (5 to10 mers) significantly better than the flexible protocol, while 2 to 4-mer poses are better predicted using the semi-rigid approach. More importantly, the semi-rigid docking protocol will likely perform better when no crystal structure information is available. They present a new parameter for parsing selective versus non-selective GAG–protein systems, which relies on two computational parameters: consistency of binding (i.e., RMSD) and docking score (i.e., GOLD Score). The new semi-rigid protocol, combined with the new computational parameter, is expected to be particularly useful in high-throughput screening of GAG sequences for identifying promising druggable targets and drug-like Hp/HS sequences.

Latest news

In biological systems, vascular networks play a pivotal role in regulating the chemical compositions of...

Amylose, a linear polymer comprised of α-1,4-linked glucopyranose units, is renowned for its propensity to...

Algae play an important ecological role as oxygen producers and carbon sequesters and are the...

Streptococcus gordonii is a Gram-positive bacterial species that typically colonizes the human oral cavity, but...