Quantum crystallographic method improves the accuracy of screening of inhibitors: A set of Alzheimer’s disease responsible protein‐ligand complexes

Background In drug design and development, identification of lead structure is a crucial step to predict the ligand binding affinity functional potency with any target enzyme/protein. The recently developed quantum crystallographic method (fragment-based approach) has been used as substitutional way calculate interaction energies. This mechanical level information gives deeper understanding structural facts position hydrogen atoms valence electron distributions. It very much essential electronic properties drug-receptor interactions. Therefore, based energy calculation better alternative docking score-based modelling. Method A set AD responsible protein-ligand complexes were selected for quantitative analysis. Molecular compounds four different enzymes (AChE/BChE/BACE1/GSK3β) was carried out then, all have subjected MD simulation. Later, 3D coordinates active site residues (around 4Å from ligand) studies. Result screened molecules are forming strong bonding hydrophobic interactions enzymes; particularly, π-π stacking, π-cationic, π-alkyl π-σ types interactions, which highly stable during dynamic behavior. After studies, energies analyzed; it ranged -20.83 -3.92 kcal/mol total each complex higher than gained And, RMSD molecule compared corresponding geometry solid-state state; found be significantly low (>0.5Å) similar. Interestingly, correlation between experimental IC50 averaged exhibits good agreement. Conclusion in-silico results revealed conformational flexibility, high stability compactness, orientation in physiological nature (water-medium). Quantum novel approach that opens new window delineate type at level. may allow us against disease.