Banca de QUALIFICAÇÃO: YAN JERÔNIMO GOMES LÔBO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : YAN JERÔNIMO GOMES LÔBO
DATE: 20/02/2024
TIME: 15:00
LOCAL: meet.google.com/exd-uuix-bkb
TITLE:

Computational Screening of the Main Protease and the S protein from SARS-CoV-2 compared to their mutants - Searching for new ligands and more efficient vaccines

KEY WORDS:

SARS-CoV-2, S protein, Molecular Modeling, Molecular Dynamics, Mobility Fingerprints, Infectivity, Immunogenicity

PAGES: 31
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUBÁREA: Química de Macromoléculas
SPECIALTY: Proteínas
SUMMARY:

INTRODUCTION: The SARS-CoV-2 virus has undergone mutations since its origin, giving rise to variants such as Delta, Gamma and Omicron. This is concerning because some variants have increased infectivity and/or decreased immunogenicity compared to the wild-type (wt) variant. Mutations in the Spike glycoprotein RBD are of particular interest due to their fundamental role in infection. OBJECTIVES: Evaluate the impact of mutations with different phenotypic groups: neutral; increased infectivity (+inf/-ev); reduced immunogenicity (-inf/+ev); phenotypes of increased infectivity and reduced immunogenicity (+inf/+ev), in RBD mobility, through the analysis of productive MD simulations of 36 RBD mutants. MATERIAL AND METHODS: The Spike wt structure was collected from the Protein Data Bank, we manually selected residues corresponding to the RBD and comparatively modeled several (36) mutants. Protonation states for all residues in each structure were estimated at a pH of 7.4 and salinity of 0.15 M. All systems were parameterized and solvated in water tanks, and were subjected to a multistep equilibrium protocol and productive 100 ns simulations in triplicate. The last 50 ns of the obtained trajectories were analyzed by mean square fluctuation per residue, cluster analysis, 2D mean square deviation, and principal component analysis. RESULTS AND DISCUSSION: Analysis of the trajectories obtained indicates that the most variable regions in the RBD are the beta1-beta2 loop of the receptor binding motif (RBM) and the 360-374 residues. There is also a tendency for the RBM to stabilize towards more favorable binding conformations in (+inf/-ev), while (-inf/+ev) presents greater conformational diversity to avoid detection by the immune system. (+inf/+ev) shows greater mobility than neutral mutants, but less mobility when compared to (-inf/+ev). Residues 360- 374 showed higher mobility in (+inf/-ev) and lower mobility in (+inf/+ev), possibly to, respectively, reduce detection and increase stability. The distribution of frames for the Omicron variant follows the pattern observed in mutants (+inf/+ev), for both regions studied.

BANKING MEMBERS:
Presidente - 2981680 - LEONARDO HENRIQUE FRANCA DE LIMA
Interno - 1367304 - ALEXSANDRO SOBREIRA GALDINO
Externo à Instituição - CARLOS HENRIQUE DA SILVEIRA