Virtual Screening of IL-6 Inhibitors for Idiopathic Arthritis

Abstract

Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by the arthritis of unknown origin and IL6 is a known target for JIA. 20 known inhibitors towards IL-6 were screened and Methotrexate (MTX) having PubChem ID: 126941 showed high binding capacity with the receptor IL-6. The similarity searching with this compound gave 269 virtual screened compounds. The said screening presented 269 possible drugs having structural similarity to Methotrexate. The docking studies of the screened drugs separated the compound having PubChem CID: 122677576 (re-rank value of-140.262). Toxicity and interaction profile validated this compound for having a better affinity with the target protein. Conclusively, this study shows that according to ADMET profile and BOILED-Egg plot, the compound (PubChem CID: 122677576) obtained from Virtual Screen could be the best drug in future during the prevention of juvenile idiopathic arthritis. In the current study, the drug CID: 122677576 is a potent candidate for treating JIA. The pharmacophore study revealed that the drug CID: 122677576 is a non-inhibitor of CYP450 microsomal enzymes and was found to be non-toxic, similar to the established drug Methotrexate (CID: 126941). It has a lower LD50 value of 2.6698mol/kg as compared to the established compound having LD50 value as 23.4955mol/kg. Moreover, the compound was found to be non-carcinogenic.

Structural insights into conformational stability of ESR1 and structure base screening of new potent inhibitor for the treatment of Breast Cancer

“…X-ray crystal structure of the ERα in complex with 4-hydroxytamoxifen (OHT)(PDB Id: 3ERT [29] was selected for the present study by considering Resolution (1.9 Å), and R-Value Free (0.262) as speci c selection parameters from the Protein Data Bank [30][31][32][33][34][35][36][37][38]. Before proceeding to dock, the PDB structure was prepared using the Protein Preparation Wizard module(Schrodinger, Inc., LLC, New York, USA) by applying criteria like removal of water molecules, assigning bond orders, lling missing hydrogens, side chains & loops, capping termini, selenomethionine to methionine reconversion, optimization and energy minimization using the OPLS-2005 force eld with default settings [39][40][41][42][43][44][45][46][47][48][49][50].…”

“…Ligand preparation was carried out on two chemical libraries (ZINC and NCI) using the LigPrep module(Schrodinger, Inc., LLC, New York, USA) for better optimization, molecular conversion from 2D to 3D, ring conformers and ionization states, tautomer states with an OPLS-2005 force eld at the pH range of 7±2 [39][40][41][42][43][44][45][46-58].…”

“…Receptor grid was generated by picking the centroid OHT's in receptor using the Receptor Grid Generation Glide module(Schrodinger, Inc., LLC, New York, USA) in the XYZ coordinates (X=31.91, Y=-1.8, Z=25.17) with default settings of the OPLS-2005 force eld and the Vander Waal's radius scaling factor of 1 Å with partial charge cut-off of 0.25Å [59][60]. Further, the ligand 4-hydroxytamoxifen (OHT) was docked into the generated grid for con rming the interaction between protein and ligand using Glide XP (Schrodinger, Inc., LLC, New York, USA)before the execution of virtual screening [39][40][41][42][43][44][45].…”

Structure-Based Virtual Screening, Molecular Docking, MolecularDynamics Simulation of VEGF Inhibitors for the Clinical Treatment of Ovarian Cancer

“…The rst cavity was recorded to hold the bound ligand earlier to its elimination and was also observed to have the largest volume and was selected for the further procedure of docking with ligands [50][51][52][53][54]. The single SDF le containing all the 12 ligands created through the LigPrep module was loaded in the docker.…”

An In silico approach for the identification of GRB2 inhibitors for the treatment of <em>Polycystic ovary syndrome</em> <em>(</em><em>PCOS</em><em>)</em>

“…This helps to develop more efficient drug candidates which would essentially help in the curing of the syndrome. The aim of the present investigation is to identify a potential GRB2 inhibitor towards the clinical treatment of Polycystic ovary syndrome (PCOS) using various molecular docking [8][9][10][11][12][13][14][15] and virtual screening approaches [16][17][18][19][20][21][22][23][24][25][26][27][28] .…”