Inhibiting brushite crystal growth: molecular docking exploration of phytoconstituents and their interaction with human serum albumin.

In our preliminary studies, the extract demonstrated inhibition of calcium phosphate (brushite) crystals. Human serum albumin (HSA) is known to act as a promoter of brushite crystal growth. Therefore, the present study aims to explore the molecular mechanisms involved in brushite crystal nephrolithiasis by conducting molecular docking of phytoconstituents from with HSA. Molecular docking is conducted on 35 phytoconstituents of against HSA, and the top five compounds are further analyzed using Induced Fit Docking (IFD) and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) methods. Molecular dynamics simulations for 50 ns are performed to assess the stability of the protein-ligand complexes. Additionally, in silico physicochemical; absorption, distribution, metabolism, excretion, and toxicity (ADME/T); and pharmacophore modeling studies are conducted. The binding pocket analysis identifies potential binding sites on HSA, and molecular docking reveals Baicalein-7-o-glucoside as the top-performing compound with a strong binding affinity. IFD and MM-GBSA support the stability of the complex. Molecular dynamics simulations indicate stable interactions over the 50 ns period. ADME/T studies suggest that the top five phytoconstituents exhibit drug-like properties with satisfactory pharmacokinetic profiles. Pharmacophore modeling generates a three-point hypothesis, and its validation indicates suitability for the HSA-Baicalein-7-O-glucoside complex. The findings from the current computational investigations indicate that polyphenolic phytoconstituents of containing the 5,6-dihydroxy chromone ring, such as Baicalein-7-O-diglucoside, may modulate the activity of HSA (PDB ID: 1E7H), potentially inhibiting the process of crystallization.