Designing Self-Inhibitory fusion peptide analogous to viral spike protein against novel severe acute respiratory syndrome (SARS-CoV-2).

COVID-19 is a highly contagious viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is declared pandemic by the World Health Organization (WHO). The spike protein of SARS-CoV-2 is a key component playing a pivotal role in facilitating viral fusion as well as release of genome into the host cell. Till date there is no clinically approved vaccine or drug available against Covid-19.

Molecular dynamics simulations and experimental studies reveal differential permeability of withaferin-A and withanone across the model cell membrane.

Poor bioavailability due to the inability to cross the cell membrane is one of the major reasons for the failure of a drug in clinical trials. We have used molecular dynamics simulations to predict the membrane permeability of natural drugs-withanolides (withaferin-A and withanone) that have similar structures but remarkably differ in their cytotoxicity. We found that whereas withaferin-A, could proficiently transverse through the model membrane, withanone showed weak permeability.

Finding potent inhibitors for COVID-19 main protease (M): an approach using SARS-CoV-3CL protease inhibitors for combating CORONA.

SARS-CoV-2 is liable for the worldwide coronavirus disease (COVID-19) exigency. This pandemic created the need for all viable treatment strategies available in the market. In this scenario, computer-aided drug design techniques can be efficiently applied for the quick identification of promising drug repurposing candidates.

Conformational perturbation of peptides in presence of polar organic solvents.

The critical role played by solvent environment in maintaining the conformational integrity of peptides and proteins is accepted without question. Numerous experiments have suggested that perturbing the solvent environment of peptides and proteins by the addition of polar organic solvents have important consequences for the conformation of these molecules. However, experimental studies of such perturbations often report different kinds of effects depending on the solvent used and/or the sequence/structure of the molecule under study.

A statistical geometry analysis of simulated water-DMSO and water-MeCN binary mixtures for biomolecular studies.

Water-Dimethylsulfoxide (DMSO) and water-Acetonitrile (MeCN) binary mixtures at various molar ratios ranging from 0 to 1 are studied using Molecular Dynamics (MD) simulations. Hydration properties of water in different regions of MeCN/DMSO are investigated by using the statistical geometry approach. The obtained results reveal that in water-DMSO simulations both water and solvent molecules prefer to be in mixed cluster forms, depending upon the concentration of DMSO.

Role of Ser65, His148 and Thr203 in the Organic Solvent-dependent Spectral Shift in Green Fluorescent Protein.

The photophysics of green fluorescent protein (GFP) is remarkable because of its exceptional property of excited state proton transfer (ESPT) and the presence of a functional proton wire. Another interesting property of wild-type GFP is that its absorption and fluorescence excitation spectra are sensitive to the presence of polar organic solvents even at very low concentrations. Here, we use a combination of methodologies including site-specific mutagenesis, absorption spectroscopy, steady-state and time-resolved fluorescence measurements and all-atom molecular dynamics simulations in explicit solvent, to uncover the mechanism behind the unique spectral sensitivity of GFP toward organic solvents.