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Research and Reviews : Journal of Computational Biology

Structure based pharmacophore Modelling of compounds against Neurodegenerative disorder – Amyotrophic Lateral sclerosis

  1. Mansi Agrawal

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the progressive degeneration of motor neurons, leading to muscle dysfunction, paralysis, and eventually death. These diseases are classified as ALS variations because autopsies reveal abnormalities in both upper and lower motor neurons. These disorders account for only 10% of all adult-onset motor neuron disease cases. Despite extensive research efforts, effective therapeutic interventions for ALS remain limited. Structure-based pharmacophore modeling have emerged as valuable computational approaches in drug discovery, offering insights into the identification and optimization of potential ALS treatments. The importance of target selection, receptor preparation, and the integration of experimental data in constructing pharmacophore models for ALS-related proteins is the core.Pharmacophore modelling is fundamentally based on the idea that the spatial arrangement of a molecule's functional groups and how they interact with the target define a molecule's biological activity. The key characteristics and spatial configuration necessary for a molecule to bind to and interact with the target are represented hypothetically in three dimensions (3D) by a pharmacophore. The compounds were selected from different literatures on the basis of their activity in IC50 on the SH-SY5Y cell lines acting against amyotrophic lateral sclerosis. The structures were optimised with respect to MMFF and then used for forming a pharmacophore hypothesis to define the active sites taking part in the bonding process to form the ligand-protein complex and provide a therapeutic effect. The hypothesis was validated with the active and decoy set to check which compound superimposes the hypothesis in the maximum degree. Maximum score of 0.71 was procured. And this hypothesis was superlative one .The process of pharmacophore modelling can be very useful for analysing and studying the further more compound that may show the maximum compatibility and binding with the target to produce more effect against the disease.

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