Unexplored regions of proteins may help fight diseases

• Grant number: 24/00654-5
• Support Opportunities: Scholarships in Brazil - Scientific Journalism
• Effective date (Start): June 01, 2024
• Effective date (End): November 30, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Raghuvir Krishnaswamy Arni
• Grantee: Peterson de Jesus Morais
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated research grant: 20/08615-8 - Protein exosites, cryptic sites and moonlighting: identification, functional mapping and effects of changes in structure, AP.TEM

Abstract

A protein is a large biological molecule composed of amino acids, folded into complex three-dimensional structures. Proteins play crucial roles in various biological functions, acting as enzymes, structural components, and signaling molecules. Proteins can have multiple roles that are still poorly understood, related to their surface, which often presents regions of secondary bindings (also known as exosites). These often unexplored regions play key roles in the regulation and modulation of various activities, ranging from gene expression, conformational stabilization, transport, inhibition, extension, modulation, and display of distinct functions. These functions can be triggered in response to changes in physicochemical conditions. Understanding exosites can provide insights into the regulation of protein activity, specificity, and the development of targeted therapies. This knowledge is crucial for advancing our understanding of various biological processes and designing drugs with greater precision and efficacy. The project to be disclosed combines high-throughput/resolution techniques, such as phage display, metabolomics, structural biology, and computational biology. Alongside these techniques, computational fragment-based methods are used to map, select, and evaluate protein surfaces and cryptic binding sites. In addition to seeking to understand specific interactions with peptides and proteins, the project aims to identify protein-protein interactions that occur under different physiological conditions. The dissemination proposal for this thematic research project is to popularize the relevance of proteins and their interactions for the general population in a more accessible and democratic way. Plural knowledge about the importance of proteins, their interactions, and applications is currently important in various areas such as medical, industrial, social, and others. The proteins studied are related to various diseases, such as viral diseases (arboviruses and COVID-19), exfoliative proteins causing necrosis, bacterial infections, venoms and toxins, and other diseases. Brazilian science has significant relevance in the production of drugs, biotechnological products, and fundamental studies, which, when popularized, can be a tool to increase investments, encourage the population to produce science, and demonstrate its importance. The produced content will be published on the social media pages of @acuriosabio, a scientific outreach page of one of the project members.