Fit Docking Research Articles

Computational screening of natural and natural-like compounds to identify novel ligands for sigma-2 receptor

ABSTRACT Sigma-2 (σ2) receptor is a transmembrane protein shown to be linked with neurodegenerative diseases and cancer development. Thus, it emerges as a potential biological target for the advancement of anticancer and anti-Alzheimer’s agents. The current study was aimed to identify potential σ2 receptor ligands using integrated computational approaches including homology modelling, combined pharmacophore- and docking-based virtual screening, and molecular dynamics (MD) simulation. Pharmacophore-based screening was conducted against a database composed of 20,523 small natural and natural-like products. In total, 1200 structures were found to satisfy the required pharmacophore features and were then exposed to docking-based screening against the generated homology model of σ2 receptor. On the basis of the pharmacophore fit scores, docking scores, and mechanism of binding interaction, 20 potential hits were retained. Five promising candidates were selected (SR84, SR823, SR300, SR413, and SR530) on the basis of their binding score and interaction. Further, in silico ADMET profiling of these compounds showed that the selected compounds possess favourable ADME properties with low toxicity risk. The mechanism of interaction of these compounds with σ2 receptor as well as their binding stability were characterized by MD simulation.

Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds

A series of hydroxylic compounds (1–10, NK-154 and NK-168) have been assayed for the inhibition of three physiologically relevant carbonic anhydrase isozymes, the cytosolic isozymes I, II and tumor-associated isozyme IX. The investigated compounds showed inhibition constants in the range of 0.068–4003, 0.012–9.9 and 0.025–115 μm at the hCA I, hCA II and hCA IX enzymes, respectively. In order to investigate the binding mechanisms of these inhibitors, in silico studies were also applied. Molecular docking scores of the studied compounds are calculated using scoring algorithms, namely Glide/induced fit docking. The inhibitory potencies of the novel compounds were analyzed at the human isoforms hCA I, hCA II and hCA IX as targets and the KI values were calculated.