In silico development of potential InhA inhibitors through 3D-QSAR analysis, virtual screening and molecular dynamics.

Tuberculosis is one of the most ancient infectious diseases known to mankind predating upper Paleolithic era. In the current scenario, treatment of drug resistance tuberculosis is the major challenge as the treatment options are limited, less efficient and more toxic. In our study we have developed an atom based 3D QSAR model, statistically validated sound with R2 > 0.90 and Q2 > 0.72 using reported direct inhibitors of InhA (2018-2022), validated by enzyme inhibition assay. The model was used to screen a library of 3958 molecules taken from Binding DB and candidates molecules with promising predicted activity value (pIC50) > 5) were selected for further analyzed screening by using molecular docking, ADME profiling and molecular dynamic simulations. The lead molecule, ZINC11536150 exhibited good docking score (glideXP = -11.634 kcal/mol) compared to standard triclosan (glideXP = -7.129 kcal/mol kcal/mol) and through molecular dynamics study it was observed that the 2nv6-complex of ZINC11536150 with Mycobacterium tuberculosis InhA (PDB entry: 2NV6) complex remained stable throughout the entire simulation time of 100 ns.Communicated by Ramaswamy H. Sarma.

In silico approach for enhancing innate lipid content of Yarrowia lipolytica, by blocking the acyl-CoA oxidase-1 enzyme, using various analogous compounds of lipids.

Yarrowia lipolytica is used as a model in this study to screen the potential candidates for inflating the innate lipid content of the cell. This study focuses on reducing the lipid degradation that occurs by the ß-oxidation process and discursively increasing the innate lipid content. Acyl-CoA oxidase-1, the primary and initial enzyme involved in the lipid degradation pathway, was selected as a target and blocked using various lipid analogous compounds. The blocking study was carried out using molecular docking and dynamic studies using computation tools. The largest active site pocket located around the Phe-394 amino acid of the target protein is taken as a site for docking. The molecular docking was performed for the selected compounds (citric acid, Finsolv, lactic acid, oxalic acid, Tween-80 and Triton X-100) and the docking results were compared with the outcome of the standard molecule (octadecatrienoic acid). Citric acid, Finsolv, Tween-80 and Triton X-100 were found to be the potential candidates for blocking the target molecule in the static condition using docking studies, revealing a minimum binding energy requirement than the standard molecule. They were further taken for a dynamics study using GROMACS software. The RMSD, RMSF, number of hydrogen bond interactions and radius of gyration of the complex molecules were studied in a dynamic approach for 100 ns. Citric acid has been found to be the potential hit compound to block acyl-CoA oxidase-1 enzyme with its maximum hydrogen interaction and minimum fluctuations. It also revealed out the minimum total energy requirement for the complex formation.

An encapsulated report on enzyme-assisted transesterification with an allusion to lipase.

Biodiesel is a renewable, sulfur-free, toxic-free, and low carbon fuel which possesses enhanced lubricity. Transesterification is the easiest method employed for the production of biodiesel, in which the oil is transformed into biodiesel. Biocatalyst-mediated transesterification is more advantageous than chemical process because of its non-toxic nature, the requirement of mild reaction conditions, absence of saponification, easy product recovery, and production of high-quality biodiesel. Lipases are found to be the primary enzymes in enzyme-mediated transesterification process. Currently, researchers are using lipases as biocatalyst for transesterification. Lipases are extracted from various sources such as plants, microbes, and animals. Biocatalyst-based biodiesel production is not yet commercialized due to high-cost of purified enzymes and higher reaction time for the production process. However, research works are growing in the area of various cost-effective techniques for immobilizing lipase to improve its reusability. And further reduction in the production cost of lipases can be achieved by genetic engineering techniques. The reduction in reaction time can be achieved through ultrasonic-assisted biocatalytic transesterification. Biodiesel production by enzymatic transesterification is affected by many factors. Various methods have been developed to control these factors and improve biodiesel production. This report summarizes the various sources of lipase, various production strategies for lipase and the lipase-mediated transesterification. It is fully focused on the lipase enzyme and its role in biodiesel production. It also covers the detailed explanation of various influencing factors, which affect the lipase-mediated transesterification along with the limitations and scope of lipase in biodiesel production.