Banca de DEFESA: FABIO JORDAO DE OLIVEIRA PEGADO

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : FABIO JORDAO DE OLIVEIRA PEGADO
DATE: 28/04/2026
TIME: 14:30
LOCAL: Google Meet
TITLE:

AlphaUnfold: Automated Structural Prediction and Stability Testing via High-Pressure Molecular Dynamics

KEY WORDS:

alphafold3, NAMD3, high-pressure molecular dinamics, protein structure prediction, protein stability, workflow automation

PAGES: 98
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

The prediction of three-dimensional protein structures has been revolutionized by the advent of AlphaFold3, which generates structural models from primary sequences accompanied by confidence metrics such as pLDDT. This work presents AlphaUnfold, an application developed to automate the structural prediction workflow and submit the resulting models to robustness tests via molecular dynamics (MD) simulations using the NAMD3 software. To optimize computational time, simulations are accelerated by GPU and the application of high pressure (1000 atm), allowing the assessment of structural stability in short 5 ns trajectories — a significant reduction compared to the conventional 200-500 ns. The results demonstrated an inverse linear correlation between the average pLDDT values and the RMSD (Root-Mean-Square Deviation) achieved in the simulations. Furthermore, it was observed that residues with low pLDDT coincide with regions of higher structural fluctuation during MD. The tool's applicability was validated in studies of protein enrichment with essential amino acids. Progressive substitutions by Arginine, guided by mCSM stability criteria, generated variants with decreasing stability, allowing AlphaUnfold to precisely determine the acceptable substitution limit. Additionally, tests were performed with myoglobin (a model protein) and phaseolin (a bean storage protein), whose stability results were promptly obtained through the automation provided by the application. The AlphaUnfold application is available on GitHub for use by the scientific community

COMMITTEE MEMBERS:
Presidente - ***.501.268-** - JOSÉ MIGUEL ORTEGA - UFMG
Interno - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN
Externo à Instituição - LUCAS BLEICHER - UFMG