Inhibiting brushite crystal growth: molecular docking exploration of <i>Enhydra fluctuans</i> phytoconstituents and their interaction with human serum albumin

In our preliminary <i>in vitro</i> studies, the <i>Enhydra fluctuans</i> 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 <i>E. fluctuans</i> with HSA. Molecular docking is conducted on 35 phytoconstituents of <i>E. fluctuans</i> 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. <i>In silico</i> 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 <i>E. fluctuans</i> 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.