In Silico Investigation against Inhibitors of Alpha-Amylase Using Structure-based Screening, Molecular Docking, and Molecular Simulations Studies.

Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase's active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes.

Nanoinformatics and Personalized Medicine: An Advanced Cumulative Approach for Cancer Management.

BACKGROUND: Even though the battle against one of the deadliest diseases, cancer, has advanced remarkably in the last few decades and the survival rate has improved significantly; the search for an ultimate cure remains a utopia. Nanoinformatics, which is bioinformatics coupled with nanotechnology, endows many novel research opportunities in the preclinical and clinical development of personalized nanosized drug carriers in cancer therapy. Personalized nanomedicines serve as a promising treatment option for cancer owing to their noninvasiveness and their novel approach. Explicitly, the field of personalized medicine is expected to have an enormous impact soon because of its many advantages, namely its versatility to adapt a drug to a cohort of patients. OBJECTIVE: The current review explains the application of this newly emerging field called nanoinformatics to the field of precision medicine. This review also recapitulates how nanoinformatics could hasten the development of personalized nanomedicine for cancer, which is undoubtedly the need of the hour. CONCLUSION: This approach has been facilitated by a humongous impending field named Nanoinformatics. These breakthroughs and advances have provided insight into the future of personalized medicine. Imperatively, they have been enabling landmark research to merge all advances, creating nanosized particles that contain drugs targeting cell surface receptors and other potent molecules designed to kill cancerous cells. Nanoparticle- based medicine has been developing and has become a center of attention in recent years, focusing primely on proficient delivery systems for various chemotherapy drugs.

An integrative docking and simulation-based approach towards the development of epitope-based vaccine against enterotoxigenic Escherichia coli.

Enterotoxigenic E.coli is causing diarrheal illness in children as well as adults with the majority of the cases occurring in developing countries. To reduce the number of cases occurring worldwide, the development of an effectual vaccine against these bacteria can be the only prevention. This conjectural work was performed using modern bioinformatics tools for investigation of proteome of ETEC strain E24377A. Different computational vaccinology approaches were deployed to assess several parameters including antigenicity, allergenicity, stability, localization, molecular weight and toxicity of the predicted epitopes required for good vaccine candidate to elicit immune response against diarrhea. We estimated two known control antigens, epitope 141STLPETTVV149 of Hepatitis B virus and epitope 265ILRGSVAHK273 of H1N1 Nucleoprotein in an attempt to corroborate our research work. Furthermore molecular docking was performed to evaluate the interaction between HLA allele and peptide, the peptide QYGGGNSAL and peptide LPYFELRWL were considered to be the most promiscuous T cell epitopes with the highest binding energy value of -2.09 kcal/mol and -1.84 kcal/mol, respectively. In addition, dynamic simulation revealed good stability of the vaccine construct as well as population coverage analysis exhibits the highest population coverage in the regions of East Asia, India, Northeast Asia, South Asia and North America. Therefore, these two epitopes can be further synthesized for wet lab analysis and could be considered as a promising vaccine against diarrhea. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-021-00287-6.