In Silico Prediction of Novel Drug Molecule for Migraine Using Blind Docking
Abstract
This study deals with a comprehensive pathway of lead molecule design for migraine focusing on the emerging in silico trends and techniques which include generation of candidate molecules, checking for their toxicity and human body likeliness, docking them with the target and ranking them based on their binding affinities. Protein sequence of Human receptor activity-modifying protein-1 (hRAMPI) was taken and prediction of missing side chain was performed using SQWRL. Energy minimization was done in Chimera using AMBER force field, followed by blind docking of the available drugs with Autodock software. Ligandscout was used to analyze the pharmacophore and its derivatives were derived using ProDRG. The derivatives were analyzed for drug-likeliness using Lipinski filters and ADME/Tox filter. Protein-ligand interactions for all the derivatives were determined using Autodock and Hex. Sumatriptan was found to be the best ligand as it had the lowest binding energy. Its 15 derivatives were drawn with minimized energy. It was found that compound number 13, 9, 10 and 12 had lowest binding energy and all had drug likeliness. In all the four compounds, ASP90A, TRP84A, ALA70A and TYR66A amino acids were found to participate in ligand-protein interaction. By the comparative analysis of the binding energies of all the complexes thus formed, three of the best ligands were chosen and analyzed for active amino acid groups mainly involved in ligand-protein interaction using Ligand Scout 2.0.…
Read the paper
Related studies
- Meta-analysis of genome-wide association for migraine in six population-based European cohorts
- New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis
- microRNA profiling in atherosclerosis, diabetes, and migraine
- Genome‐Wide‐Associated Variants in Migraine Susceptibility: A Replication Study From North I ndia
- Pharmacoinformatics elucidation of potential drug targets against migraine to target ion channel protein KCNK18
- Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.