In silico studies of the interaction of antimicrobial peptides with proteins from microorganisms by target fishing and docking approaches

• Grant number: 24/09317-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2024
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Katia da Conceição
• Grantee: Gabriele Santos Cepinho
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil

Abstract

Infections caused by antibiotic-resistant bacteria are among the leading causes of death for people of all ages, revealed by a global study on antimicrobial resistance (AMR). Peptides and peptidomimetics are re-emerging as candidates in the development of therapeutic strategies due to their specificity and low toxicity. In this context, a strategy for the design and optimization of peptides/peptidomimetics combines computational approaches, from structural bioinformatics to atomistic simulations. In the present project, new peptides designed from cecropins and cathepsins sequences with potential broad-spectrum activity and cell penetration will be investigated for their ability to bind proteins. A pipeline guided by a computational database for rational analysis and modification will be used to optimize these peptide structures, aiming to improve their efficacy and selectivity. They will then be investigated, through target fishing, the possible protein molecular targets for binding with the selected peptides, using different web servers. The stability and binding affinity to peptide-protein targets will be evaluated through molecular docking. Based on the obtained information, an in-depth analysis will be conducted based on the literature, with the aim of categorizing and examining the identified targets and better understanding the mechanisms involved in the activities of the selected peptides.