MD simulations for rational design of high-affinity HDAC4 inhibitors - Analysis of non-bonding interaction energies for building new compounds.

This study investigates the contributions of non-bonding energy (NBE) to the efficacy of four HDAC4 co-crystallized inhibitors (HA3, 9F4, EBE, and TFG) through 100ns Molecular Dynamics (MD) simulations. These inhibitors contain hydroxamic acid (HA3, 9F4, EBE) or diol (TFG) as zinc-binding groups. In PDBs 2VQJ and 2VQM, the HDAC4 catalytic domain is in the 'open' conformation, while in PDBs 4CBT and 6FYZ, the same is in the 'closed' conformation.

Molecular Dynamics Simulations of HDAC-ligand Complexes Towards the Design of New Anticancer Compounds.

Quantitative Structure-activity Relationship (QSAR) studies gained a foothold in the mid-1960s to rationalise the biological activity of medicinally important compounds. Since then, the advancements in computer hardware and software added many new techniques and areas to this field of study. Molecular dynamics (MD) simulations are one such technique in direct drug design approaches.

Conformational perturbation of SARS-CoV-2 spike protein using N-acetyl cysteine: an exploration of probable mechanism of action to combat COVID-19.

The infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in a pandemic with huge death toll and economic consequences. The virus attaches itself to the human epithelial cells through noncovalent bonding of its spike protein with the angiotensin-converting enzyme-2 (ACE2) receptor on the host cell. Based on studies we hypothesized that perturbing the functionally active conformation of spike protein through the reduction of its solvent accessible disulfide bonds, thereby disintegrating its structural architecture, may be a feasible strategy to prevent infection by reducing the binding affinity towards ACE2 enzyme.

Effect of mode of administration on Edinburgh Postnatal Depression Scale in the South Indian population: A comparative study on self-administered and interviewer-administered scores.

Background: Edinburgh Postnatal Depression Scale (EPDS) is a validated screening tool widely used to assess perinatal depression (PND). However, due to stigma associated with PND, respondents could answer sensitive questions differently depending on the mode of administration, especially in culturally and linguistically diverse country like India. The present study explored longitudinal differences in EPDS scores between self-administered and interviewer-administered modes.

Non-bonding energy directed designing of HDAC2 inhibitors through molecular dynamics simulation.

Designing an inhibitor having strong affinity in the active site pocket is the cherished goal of structure based drug designing. To achieve this, it is considerably important to predict which structural scaffold is better suited for change to increase affinity. We have explored five HDAC2 co-crystals having PDB ligand code- (vorinostat), , , (BRD4884) and (BRD7232).