An in silico Appraisal to Identify High Affinity Anti-Apoptotic Synthetic Tetrapeptide Inhibitors Targeting the Mammalian Caspase 3 Enzyme

Abstract

Apoptosis is a general phenomenon of all multicellular organisms and caspases form a group of important proteins central to suicide of cells. Pathologies like cancer, Myocardial infarction, Stroke, Sepsis, Alzheimer's, Psoriasis, Parkinson and Huntington diseases are often associated with change in caspase 3 mediated apoptosis and therefore, caspases may serve as potential inhibitory targets for drug development. In the present study, two series of synthetic acetylated tetrapeptides containing aldehyde and fluromethyl keto groups respectively at the C terminus were proposed. All these compounds were evaluated for binding affinity against caspase 3 structure. In series 1 compound Ac-DEHD-CHO demonstrated appreciable and high binding affinity (Rerank Score: -138.899) against caspase 3. While in series 2 it was Ac-WEVD-FMK which showed higher binding affinity (Rerank Score: -139.317). Further these two compounds met ADMET properties and demonstrated to be nontoxic.

Identification of High-Affinity Small Molecule Targeting IDH2 for the Clinical Treatment of Acute Myeloid Leukemia

“…The molecular docking studies was performed by using Molegro Virtual Docker (MVD) which is unified with high potential Piece Wise Linear Potential (PLP) and MolDock scoring function (Kelotra et al, 2014b;Bandaru et al, 2014;Khandekar et al, 2016;Bandaru et al, 2013). Subsequently, all cavities were detected to get high volume cavity and hence the highest volume cavity (>2000Å) was selected for docking and to target the active of the IDH2 structure (PDB ID: 5SVN) with the pre-prepared 4 ligands.…”

Design of novel JAK3 Inhibitors towards Rheumatoid Arthritis using molecular docking analysis

“…Using Molegro Virtual Docker (MVD), which unified high potential Piece-Wise Linear Potential (PLP) and MolDock scoring function [30-33], molecular docking analyses were carried out. The protein was first loaded in the Docker where it was prepared by removing the pre-existing ligand from the protein structure [34-36]. Cavity one was witnessed to possess the largest volume and the ligand structure docked within it and was thence utilized for docking of the prepared ligands [37-41].…”

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] .…”