Banca de QUALIFICAÇÃO: ANA FRANCISCA TEIXEIRA GOMES

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : ANA FRANCISCA TEIXEIRA GOMES
DATE: 27/02/2023
TIME: 09:00
LOCAL: Sala de aula 06 do Departamento de Nutrição
TITLE:

In silico study of therapeutic targets in the treatment of Diabetes Mellitus: A systematic review and analysis of a peptide derived from tamarind trypsin inhibitor

KEY WORDS:

Computer Simulation. Peptides. Hypoglycemic Agents. Receptor, Insulin. Therapeutics.

PAGES: 84
BIG AREA: Ciências da Saúde
AREA: Nutrição
SUMMARY:

Diabetes Mellitus (DM) is one of the most prevalent metabolic disorders in the world, with a growing search for natural, safe and effective therapeutic agents, especially food peptides. Through bioinformatics tools, the discovery of interaction mechanisms between molecules and their possible targets is optimized. This work aimed to present targets used in in silico studies related to glycemic control through a systematic review (SR) and an in silico study with a peptide derived from trypsin inhibitor isolated from tamarind seeds (TTI). The protocol was elaborated following the recommendations of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), registered in PROSPERO (CRD42022353808) and published. In the ongoing SR, studies that meet the PECo strategy (Problem, exposure, context) were included. In the ongoing SR, studies that meet the PECo strategy (Problem, exposure, context) were included. The databases used were: Medline (PubMed); Web of Science; Scopus; Base; ScienceDirect; Virtual Health Library (VHL). A total of 1878 articles were identified, including 16 articles referring to original in silico studies that used therapeutic targets for the treatment of DM and that validated the use of these targets in vivo. The risk of bias will be assessed using a checklist based on Strengthening the reporting of empirical simulation studies (STRESS). To obtain the TTI, trypsin-sepharose affinity chromatography was used, characterized by SDS-PAGE gel and antitryptic activity. The TTI was hydrolyzed in vitro using a protocol adapted from INFOGEST, simulating the oral, gastric and intestinal phases and monitoring the enzymatic susceptibility pattern using SDS-PAGE gel. The theoretical model of the purified tamarind seed trypsin inhibitor (TTIp 56/287) was cleaved in silico, being selected for simulation by molecular dynamics, Peptideotripchymo59 for presenting the most negative score of the docking score (-175.53) with the insulin receptor (IR) (PDB ID 4OGA). Peptideotripchymo59 showed affinity and stability in complex with the IR reaching equilibrium at the beginning of the simulation, in addition, the amino acid residues Arginine at position 16 (-209.07 kJ mol-1), Threonine at position 1 (-148, 54 kJ mol-1) and valine in position 2 (-94.53 kJ mol-1) that interacted the most, with the site of interaction with the IR being in the same binding site, but in a different region from that in which insulin interacted how to IR. It is suggested that Peptideotripchymo59 may be an insulin mimetic molecule, being a possible candidate as a therapeutic agent for the treatment of type 1 and 2 DM.

COMMITTEE MEMBERS:
Presidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externo ao Programa - 1959889 - DAVI SERRADELLA VIEIRA - nullExterna ao Programa - 2665457 - GIDYENNE CHRISTINE BANDEIRA SILVA DE MEDEIROS - null