Banca de QUALIFICAÇÃO: CAROLINA ARRUDA BRAZ

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE: CAROLINA ARRUDA BRAZ
DATA: 01/09/2015
HORA: 09:00
LOCAL: SALA DE AULA II DO PPGCF
TÍTULO:

4D-LQTA QSAR OF PLASMODIUM FALCIPARUM PLASMEPSIN II
INHIBTORS.


PALAVRAS-CHAVES:

malaria, lqta-qsar, plasmpsin II, 4D QSAR


PÁGINAS: 36
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Abstract
Malaria represents an actual scenario of importance for Drug Discovery. Plasmodium falciparum, the most
virulent form of the parasite, adds the increasing resistance of the current therapy to the issue. Plasmepsin
II is part of a group of aspartic protease responsible for Plasmodium's metabolism of hemoglobin,
representing a potential pharmaceutical target for malaria inhibition. The repertoire of inhibiting
compounds from plasmepsin II were used to build a QSAR models. Molecular Dynamics was performed
previously, to better understand potential inhibitors biding mode and to compose the construction of the
predicting model. The simulation occurred using GROMACS, AMBER99SB-ILDN force field with
implicit solvent. The system was submitted to geometry optimization using steepest descent and to
molecular dynamics simulation with 2000 ps using GROMACS package. The LQTA-QSAR model was
obtained by calculating Coulomb and Lennard-Jones descriptors from the aligned conformations with
Open3DQSAR. The model was built using 37 samples with 10 variables and 2 latent variables using PLS
regression models. The model obtained a Q²:0.92; R²: 0.95 and a prediction Q²: 0.78 from a test set with 12
molecules. With a better understanding of the biding mode through molecular dynamics, it was possible to
reach better results on constructing a 4D predicting model instead of a 3D, mainly due to the difficulty
presented by the protein flexibility. The model has good statistics, robustness (by Leave-N-out-tests) and
can be used to predict the activity of proposed Plasmepsin II inhibitors.


MEMBROS DA BANCA:
Presidente - 2087759 - ANDRE DUCATI LUCHESSI
Interno - 1218940 - ANTONIA CLAUDIA JACOME DA CAMARA
Externo ao Programa - 1714867 - CAIO LIMA FIRME
Notícia cadastrada em: 20/08/2015 11:32
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