Systematic analysis to identify novel disease indications and plausible potential chemical leads of glutamate ionotropic receptorNMDAtype subunit 1,GRIN1

Abstract

Schizophrenia is a mental illness affecting the normal lifestyle of adults and early adolescents incurring major symptoms as jumbled speech, involvement in everyday activities eventually got reduced, patients always struggle with attention and memory, reason being both the genetic and environmental factors responsible for altered brain chemistry and structure, resulting in schizophrenia and associated orphan diseases. The network biology describes the interactions among genes/proteins encoding molecular mechanisms of biological processes, development, and diseases. Besides, all the molecular networks, protein‐protein Interaction Networks have been significant in distinguishing the pathogenesis of diseases and thereby drug discovery. The present meta‐analysis prioritizes novel disease indications viz. rare and orphan diseases associated with target Glutamate Ionotropic Receptor NMDA Type Subunit 1, GRIN1 using text mining knowledge‐based tools. Furthermore, ZINC database was virtually screened, and binding conformation of selected compounds was performed and resulted in the identification of Narciclasine (ZINC04097652) and Alvespimycin (ZINC73138787) as potential inhibitors. Furthermore, docked complexes were subjected to MD simulation studies which suggests that the identified leads could be a better potential drug to recuperate schizophrenia.

Investigating the potential of Juglans regia phytoconstituents for the treatment of cervical cancer utilizing network biology and molecular docking approach

“…One thousand-four phytochemicals passed the R05 drug-likeness filter. The 3D structures of the druglike phytochemicals were then energy-minimized using the OpenBabel toolbox’s obminimize [ 20 ]. Finally, OpenBabel was used to transform the ligands’ energy-minimized 3D structures.sdf to.…”

Proteomics based systematic exploration of the peptidoglycan biosynthesis of Olsenella uli DSM 7084 towards pathogenesis

“…Drugs iterated from DrugBank in SDF format for the concerned drug target were utilized for docking. PDB les were converted into PDBQT les by assigning Kollman charges and hydrogen atoms [22,23,24]. A grid of 70 x 70x 70 for x, y and z coordinates, respectively were taken and centered at the binding pockets identi ed by PockDrug software [25,26].…”

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

“…Over the last decade, there has been a rapid increase in CADD-based studies of depression, including docking studies of ligands for serotonin reuptake [171,172], MAO A and MAO B [173,174], dual action on MAO-B/AChE [175], glycogen synthase kinase [176], sodium hNaV1.2 or hNaV1.7 channels [177], serotonin receptors (5HT1A, 5-HT2A, 5-HT2C and 5-HT4) [171,[178][179][180][181], adenosine A1/A2A receptors [182], T-type calcium channels [183], tryptophan 2,3-dioxygenase [184] and sigma receptor [185]. Similarly, application of docking in psychoses involved ligands for serotonin 5HT2 and dopamine D2 receptors [186], α4β2 and α7 nicotinic acetylcholine receptors [187,188], phosphodiesterase 10A [189], MAO A and B [190], a syntaxin-binding protein (STXBP1) [191], NMDA type subunit 1 (GRIN1) [192], fatty acid binding protein 7 (FABP7) [193,194], metabotropic glutamate mGluR5 receptor [195], ionotropic GABA-A receptor [196], glycine transporter type 1 (GlyT1) [197] and kynurenine aminotransferase II (KATII) [198].…”