A vast network of genes is inter-linked through protein-protein interactions and is critical component of almost every biological process under physiological conditions. Any disruption of the biologically essential network leads to pathological conditions resulting into related diseases. Therefore, proper understanding of biological functions warrants a comprehensive knowledge of protein-protein interactions and the molecular mechanisms that govern such processes. The importance of protein-protein interaction process is highlighted by the fact that a number of powerful techniques/methods have been developed to understand how such interactions take place under various physiological and pathological conditions. Many of the key protein-protein interactions are known to participate in disease-associated signaling pathways, and represent novel targets for therapeutic intervention. Thus, controlling protein-protein interactions offers a rich dividend for the discovery of new drug targets. Availability of various tools to study and the knowledge of human genome have put us in a unique position to understand highly complex biological network, and the mechanisms involved therein. In this review article, we have summarized protein-protein interaction networks, techniques/methods of their binding/kinetic parameters, and the role of these interactions in the development of potential tools for drug designing.
Mycobacterium tuberculosis is the causative agent of the
disease, tuberculosis and H37Rv is the most studied clinical strain. We use
comparative genome analysis of Mycobacterium tuberculosis H37Rv
and human for the identification of potential targets dataset. We used DEG
(Database of Essential Genes) to identify essential genes in the H37Rv strain.
The analysis shows that 628 of the 3989 genes in Mycobacterium
tuberculosis H37Rv were found to be essential of which 324 genes
lack similarity to the human genome. Subsequently hypothetical proteins were
removed through manual curation. This further resulted in a dataset of 135
proteins with essential function and no homology to human.
Angiogenin (ANG) protein plays a crucial role in angiogenesis, neovascularization, and cancer metastasis in NSCLC (non‐small cell lung cancer) via non‐coding tiRNA. It protects the cell under ER (endoplasmic reticulum) stress‐induced apoptosis through the translational reprogramming process. Although B82 (Curcumin derivatives) induces ER stress‐induced apoptosis, its mechanism of action was not studied. Therefore, it was hypothesized that the ribonucleolytic activity of ANG may be regulated by B82, resulting in modulated ER stress signaling for apoptosis. Hence, we designed and proposed a synthesis scheme for RNA‐based anti‐angiogenic derivatives of 2‐deoxyuridine nucleoside forming peptide bond with amino acids like serine (Ser‐3) and para‐hydroxy‐phenyl glycine (Normtyr‐1) and compared B82 with them to know the binding affinity with ANG, anti‐angiogenic potential, and its probable mechanism of anti‐RNase activity through MD simulation study. Therefore, using Gromos96 43a1 and 43a2 force fields, MD simulation was performed to investigate binding affinity, ligand‐induced molecular surface area change, conformational change, and dynamics of catalytic site residues to predict ligand binding to ANG in this study. The obtained binding free energy (∆Gbind) result showed the total average ∆Gbind as −113.480 ± 1.682 (Normtyr‐1) > −53.038 ± 33.069 (B82) > −27.909 ± 16.438 (Ser‐3) kJ/mole specify role of B82 in regulating ER stress signaling induced apoptosis through ANG ribonucleolytic activity inhibition, suitability of 43a2 force fields and methodology in ligand screening. It shows the crucial role of Leu115 and His13 residue involvement in total ∆Gbind contribution. Hence, based on the MD result, novel conformation of catalytic residues, and ∆Gbind, a promising combination candidate could be proposed for metastatic NSCLC therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.