Banca de QUALIFICAÇÃO: WENDJILLA FORTUNATO DE MEDEIROS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : WENDJILLA FORTUNATO DE MEDEIROS
DATE: 20/03/2023
TIME: 09:00
LOCAL: Salão de reuniões do DNUT - Primeiro andar
TITLE:

THERAPEUTIC TARGETS OF OBESITY AND IN SILICO POTENTIAL OF TRYPSIN INHIBITORS ISOLATED FROM TAMARIND SEEDS AS PRECURSOR OF LIPASE INHIBITORS PEPTIDES

KEY WORDS:

Computer Simulation, Hydrolases, Therapeutics, Anti-Obesity Agents, Tamarindus indica L. 

PAGES: 70
BIG AREA: Ciências da Saúde
AREA: Nutrição
SUMMARY:

Obesity is a multifactorial disease with numerous therapeutic targets and diverse cardiometabolic implications. Despite the existence of approved medications for its treatment, the search for new alternatives is essential cosidering the side effects of drugs, low efficacy and the consequent progression of numbers. This study aims to identify therapeutic targets for obesity studied in silico through a systematic review and to evaluate the potential of peptides derived from trypsin inhibitor isolated from tamarind seeds (ITT) to interact in silico with Human Pancreatic Lipase (LPH). The systematic review was guided by the following research question “What therapeutic targets have been used in in silico analysis for the treatment of obesity?” Which was structured based on the acronym PECo (P, problem; E, exposure; Co, context). A review protocol was developed, which was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) under the number CRD42022353808 according to the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and the systematic review was developed in accordance with the PRISMA. The selection was carried out in accordance with the eligibility criteria, according to PECo. The databases used were PubMed, ScienceDirect, Scopus, Web of Science, BVS and EMBASE. The application of search strategies returned 937 articles, to be evaluated for eligibility for inclusion. Selected articles will be assessed for risk of bias using an adapted checklist and will proceed to data extraction and synthesis. For the computational simulation studies, the in silico hydrolysis of ITTp (ITTp 56/287) was performed with the ExPASy PeptideCutter tool. Five peptides were selected for modeling on the trRosetta server and evaluated for their bioactivity potential (PeptideRanker), cell penetration (CellPPD) and half-life (HLP). Molecular docking studies were conducted between (ITTp 56/287), the modeled peptides and the drug Orlistat (control) to identify their interaction with LPH (PDB ID:1LPB). The peptide identified with the greatest potential for inhibition of LPH followed for the study of Molecular Dynamics (DM) with LPH, conducted in the GROMACS software. The peptides studied did not show cell penetration capacity, however PEP2 and PEP4 were classified as potential bioactive peptides. PEP2 also showed high stability and the longest half-life in a simulated intestinal environment (1,863 seconds). Docking studies resulted in scores of -136.13 and -183.25 for PEP2 and PEP4, respectively, however PEP2 was more promising when interacting with amino acids in the regions of interest in the catalytic pocket and hydrophobic lid. The DM revealed a good interaction of PEP2 with LPH, showing interaction potential energy (EPI) of -628.44 kJ mol-1, highlighting four PEP2 residues that were responsible for 74.3% of the EPI (Asp3, Ser1, Asp4 and Asp5). It is then expected to contribute to the identification of experimental and/or theoretical models of the most promising targets for the treatment of obesity, assisting in the design of bioinformatics studies, as well as understanding the potential application of ITTp and its derived peptides as an anti-obesity molecule providing basis for future in vitro and/or in vivo studies.

COMMITTEE MEMBERS:
Presidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Interna - 2646462 - BRUNA LEAL LIMA MACIEL
Externo ao Programa - 1893445 - EUZEBIO GUIMARAES BARBOSA - null