Banca de QUALIFICAÇÃO: EDUARDO GABRIEL AMARAL DE OLIVEIRA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE: EDUARDO GABRIEL AMARAL DE OLIVEIRA
DATA: 30/03/2026
HORA: 13:00
LOCAL: http://meet.google.com/bvj-dswz-zoe
TÍTULO:

Manipulating Conformational Dynamics and Spectroscopic Probe Behavior under Pressure and Solvent Effects: Insights into MALT1 Function and Novel Diagnostic Strategies

PALAVRAS-CHAVES:

Molecular dynamics, MALT1, metastable state, pressure, enhanced sampling

PÁGINAS: 81
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Físico-Química
RESUMO:

The MALT1 protein is an important regulator of cell death in the human body,
and it’s ability to balance NF-κβ factor is assotiated to both reaction pathways it par-
ticipates while inside the CBM complex. A disfunctional NF-κβ regulation is reported to
lead to autoimmune diseases, and the Resistant Crustose Scabies Infection being charac-
terized by an abnormality in MALT1’s structure after it had undergone a mutation in the
terminal Ig region points to a relation between them. This study employed an enhanced
sampling methodology consisting of On-the-fly Probability Enchanced Sampling, Replica
Exchange and pressure variations to sample the conformational space of both wild-type
and mutant MALT1, allowing a fine exploration of the metastable states it could be found
at, as well as the folding and unfolding events. Results show that while the wild-type pro-
tein experience an increase in the populations as pressure was increased, flattening their
histograms, the mutated counterpart experienced the opposed effect, with the less poplu-
ated metastable states becoming less visited in the space around the most stable state,
with an energy barrier close to RT to the second most populated mestastate. It was also
found that the mutated high pressure conformations had less resemblancies to their high
pressure counterparts from the wild-type simulations than their lower pressure analogues,
point that the single residue mutation produced big differences in the FES of the proteins’s
conformations. Finally, it was observed very little changes in MALT1’s catalytic cysteine
between the two proteins, while the mutated residue and it’s analogue in the wild-type’s
contact patterns change dramatically, point out that the mutation should disturb CBM’s
scaffolding pathway, while the proteolytic activity remains the unaltered.

MEMBROS DA BANCA:
Presidente - TEODORICO DE CASTRO RAMALHO (Membro)
Externo à Instituição - TAINÁH MARTINS RESENDE SANTOS - UFLA (Membro)
Externo à Instituição - MATEUS AQUINO GONÇALVES - UEMG (Membro)
Externo à Instituição - GUNAR VINGRE DA SILVA MOTA - UFPA (Membro)
Externo ao Programa - ELAINE FONTES FERREIRA DA CUNHA - DQI/ICN (Suplente)