Banca de QUALIFICAÇÃO: EMANUELLY KARLA ARAUJO PADILHA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : EMANUELLY KARLA ARAUJO PADILHA
DATE: 27/08/2024
TIME: 09:00
LOCAL: Sala da direção do IQB
TITLE:

Computational Investigation of the Catalytic Mechanism of nsP2 of the Chikungunya Virus (CHIKV) 

KEY WORDS:

Cysteine protease; nsP2; Chikungunya.

PAGES: 60
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUMMARY:

The nsP2 protein of the Chikungunya virus (CHIKV), a cysteine protease, is an essential enzyme for the viral life cycle. Therefore, understanding the function of this enzyme at the molecular level is crucial for the future development of new inhibitors. In this dissertation, we exclusively investigate the enzymatic mechanism of nsP2. We employed Molecular Dynamics (MD) simulations and a cluster approach, a methodology that utilizes Quantum Mechanics (QM), to study the enzymatic reaction in the active site of nsP2, specifically the deprotonation of the Cys478 residue by the His548 residue. Additionally, we considered how the presence of a water molecule might catalyze this reaction. Our results indicate that the presence of this water molecule assists in the formation of the Cys− His+ ion pair. These calculations provided a comprehensive picture of the possible reaction pathways for this enzyme, including details of the reaction mechanism and the corresponding activation barriers. Detailed knowledge of the enzymatic target is fundamental for the development of effective inhibitors, as it allows the identification of critical points in the enzyme's mechanism of action that can be exploited to create molecules that specifically interfere with the target's function. This molecular understanding provides a solid foundation for the rational design of future inhibitors with potential applications in the treatment of CHIKV fever. Continuous research into the enzymatic mechanism and the interaction between the nsP2 active site and potential inhibitors will be critical for developing effective antiviral therapies.

COMMITTEE MEMBERS:
Presidente - 3182336 - EDEILDO FERREIRA DA SILVA JUNIOR
Interno(a) - 2343745 - JULIO COSME SANTOS DA SILVA
Externo(a) à Instituição - ROBERTA PEREIRA DIAS
Interno(a) - 1366289 - THIAGO MENDONCA DE AQUINO