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Enhancing Docking Accuracy Through Flexible Pocket-Based Validation: A Case Study On 1eag
Abstract
Accurate definition of the binding pocket is a crucial step in ensuring the reliability of molecular docking simulations. Precise pocket definition is fundamental to achieving reliable docking predictions, yet few studies have established a reproducible protocol for pocket-based validation on fungal proteases. This study focuses on the structural characterization of the 1EAG protease active site as a preliminary stage for flexible docking validation. The three-dimensional structure of 1EAG was analyzed to identify key active-site residues within 3–5 Å of the co-crystallized ligand (A70). Twelve residues were identified, comprising polar/ionic (58%), hydrophobic (25%), and aromatic (17%) types. These residues were further classified according to their functional interactions, including hydrogen bonding, π–π stacking, and hydrophobic contacts. A simplified pharmacophore model highlighting donor, acceptor, aromatic, and hydrophobic features was constructed to represent the spatial organization of the pocket. The results demonstrate that ASP32 serves as the catalytic hotspot, TYR84 and TYR225 stabilize the ligand through π–π interactions, and hydrophobic residues (ILE and LEU) form the outer pocket contour. Although the present analysis is limited to static pocket characterization, it provides a reproducible framework for the rational development of flexible docking validation protocols.
Keywords: molecular docking, pharmacophore modeling, receptor flexibility, 1EAG, Candida albicans.
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DOI: http://dx.doi.org/10.52155/ijpsat.v54.1.7630
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