Exploit water interactions in your ligand design

Water molecules play a very important role in biochemical processes beyond acting as mere solvents. The presence and stability of water molecules in a binding pocket can strongly influence the interactions between a protein and ligand. Identifying regions of low water stability in your protein of interest enables you to target these areas to gain additional potency and selectivity in your ligands. Therefore, understanding and exploiting water stability analysis is a crucial aspect in successful structure-based design.

One of the water analysis methods implemented in Cresset’s comprehensive molecule design platform, Flare™, is Grid Inhomogeneous Solvent Theory (GIST). GIST uses a restrained molecular dynamics simulation to compute the distributions and thermodynamics of water molecules in a given volume. It can be used on both apo proteins and ligand-protein complexes to generate heat surface maps that highlight regions of high and low water stability. GIST water analysis is a useful tool to reveal hydration sites and to guide computer-aided molecule design, with applications in docking, QSAR analysis and Free Energy Perturbation (FEP) calculations.

Discover how GIST provides insights into the detailed energetics of water binding by viewing our webinar ‘Exploit water interactions in your ligand design: Using GIST to analyze water stability in the binding pocket’. Request a recording to explore how GIST works, see examples of the outcomes that you receive and learn how to interpret the results.

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