Fragment-based design and MD simulations of human papilloma virus-16 E6 protein inhibitors.

The main objective of this study is to screen potential small molecule inhibitors against HPV (Human Papilloma Virus)-16 E6 protein (HPV16 E6P) using a fragment-based approach. Twenty-six natural HPV inhibitors were selected based on the review of the literature. Among them, Luteolin was selected as the reference compound. These 26 compounds were used to generate novel inhibitors against HPV16 E6P. Fragment script and BREED of Schrodinger software were used to build novel inhibitor molecules. The result in 817 novel molecules was docked into the active binding site of HPV E6 protein and the top ten compounds were screened based on binding affinity compared to Luteolin for further study. Compounds Cpd5, Cpd7, and Cpd10 were the most potent inhibitors of HPV16 E6P and these were non-toxic and showed high Gastrointestinal (GI) absorption and positive drug-likeness score. Complexes of these compounds were stable in the 200 ns Molecular Dynamics (MD) simulation. These 3 HPV16 E6P inhibitors could be the lead molecules as new drugs for HPV-related diseases.Communicated by Ramaswamy H. Sarma.

Microbial roles in the terrestrial and aquatic nitrogen cycle-implications in climate change.

Nitrogen, as an essential component for living organisms, is the primary limiting nutrient on Earth. The availability and effective utilization of nitrogenous compounds for metabolic and other essential biochemical reactions are dependent on the myriad and phylogenetically diverse microbial communities. The microorganisms harmoniously interact and participate in every reaction of the nitrogen cycle to continuously transform nitrogen into its various bio-available forms. Research on the nitrogen cycle continues to disclose that there are many reactions that remain unknown. In this review, we summarize the recent discoveries that have contributed to advancing our understanding of the microbial involvement in reactions of the nitrogen cycle in soil and aquatic systems that influence climate change. Additionally, the mini-review highlights, which anthropogenic activities cause disturbances in the nitrogen cycle and proposes how beneficial microbes may be harnessed to replenish nitrogen in agricultural ecosystems.