RESUMEN
The leading cause of death worldwide is cancer. Although there are various therapies available to treat cancer, finding a successful one can be like searching for a needle in a haystack. Immunotherapy appears to be one of those needles in the haystack of cancer treatment. Immunotherapeutic agents enhance the immune response of the patient's body to tumor cells. One of the immunotherapeutic targets, Cluster of Differentiation 47 (CD47), releases the "don't eat me" signal when it binds to its receptor, Signal Regulatory Protein (SIRPα). Tumor cells use this signal to circumvent the immune system, rendering it ineffective. To stop tumor cells from releasing the "don't eat me" signal, the CD47-SIRPα interaction is specifically targeted in this study. To do so, in silico peptides were designed based on the structural analysis of the interaction between two proteins using point mutations on the interacting residues with the other amino acids. The peptide library was designed and docked on SIRPα using computational tools. Later on, after analyzing the docked complex, the best of them was selected for MD simulation studies of 100 ns. Further analysis after MD studies was carried out to determine the possible potential anti-SIRPα peptides.
RESUMEN
BACKGROUND: Although water is regarded as a simple molecule, its ability to create hydrogen bonds makes it a highly complex molecule that is crucial to molecular biology. Water molecules are extremely small and are made up of two different types of atoms, each of which plays a particular role in biological processes. Despite substantial research, understanding the hydration chemistry of protein-ligand complexes remains difficult. Researchers are working on harnessing water molecules to solve unsolved challenges due to the development of computer technologies. OBJECTIVES: The goal of this review is to highlight the relevance of water molecules in protein environments, as well as to demonstrate how the lack of well-resolved crystal structures of proteins functions as a bottleneck in developing molecules that target critical therapeutic targets. In addition, the purpose of this article is to provide a common platform for researchers to consider numerous aspects connected to water molecules. CONCLUSION: Considering structure-based drug design, this review will make readers aware of the different aspects related to water molecules. It will provide an amalgamation of information related to the protein environment, linking the thermodynamic fingerprints of water with key therapeutic targets. It also demonstrates that a large number of computational tools are available to study the water network chemistry with the surrounding protein environment. It also emphasizes the need for computational methods in addressing gaps left by a poorly resolved crystallized protein structure.