Banca de DEFESA: JOSE XAVIER DE LIMA NETO

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : JOSE XAVIER DE LIMA NETO
DATA : 04/01/2019
HORA: 14:00
LOCAL: Sala da Física - Departamento de Biofísica
TÍTULO:

Quantum Biochemistry of Medicinal Drugs


PALAVRAS-CHAVES:
gpcrs, mfcc, interactionenergy, serotonin, gaba, imunotherapy

PÁGINAS: 140
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
RESUMO:
The drug development process have been improved by the add of 
other knowledge areas in the field of pharmaceutical sciences. 
Among these improvements, the introduction of the computational 
simulation was, with no doubt, one of the greatest landmarks for 
the field’s development. Nowadays, there are two main targets in 
drug development, the G protein-coupled receptors (GPCRs) and 
the immunotherapeutics. 5-HT1B receptors have been targeted for 
the treatment of migraine, since they act in the brain arteries 
contraction. By the other hand, class C GPCRs are potent 
neuromodulators, though small attention has been dedicated to 
them, such as the GABAB receptors. These receptor acts as potent 
inhibitors of the neuronal signal, leadind to impairments in the 
neurotransmitters release and closure of ionic channels. Despite its 
pharmacological relevance, only baclofen is approved by US-FDA as 
a molecule targeting GABAB, being used to treat neuropathic pain. 
For the class of immunotherapeutics, the most remarkable are the 
monoclonal antobodies (mAtb) which impair the binding between 
checkpoint proteins of T cells and their ligands in cancer cells. The 
main target for these mAtb is the programmed cell death protein 1 
(PD-1) and its ligands, PD-L1 and PD-L2. In this sense, this work 
propose a quantum biochemistry evaluation of the interactions 
made by compound thar act in 5-HT1B, PD-1 e GABAB receptors 
aiming to deepen the knowledge and describe the key points for the
 docking and stabilization of these compunds within the binding site. 
Thus, we take into account the crystallographic structure of the 
three receptors, which were fractionated in amino-acid residues by 
the molecular fractionation with conjugate caps (MFCC) scheme for 
posterior quantum (DFT) calculation. By our results, it was possible 
to predict the relevance of the amino-acids that compose the 
binding site for the three receptors, including the residues ASP129, 
ASP352, ASP123, GLU198, ASP204, PHE330, LEU126, PHE351, 
ILE130, VAL201, VAL200, THR355 e ARG114, that are part of the 
binding site for dihydroergotamine-5-HTR complex, the residues 
SER130, GLY151, SER153, HIS170, TYR250, TRP278, GLU349,
VAL201, SER152, SER154, GLN348, ARG168 e TRP65, which 
compose the GABAB’s binding site for GABA, baclofen, SCH50911 
and 2-hydroxysaclofen, as well as the lisine residue K131 from PD-1
 as the most relevant for the coupling of pembrolizumab, nivolumab 
and PD-L1. These residues shown the most intense attraction of 
repulsion energies, forming the key point for the ligand’s anchoring 
and stabilization. Through these data, it was possible to identify and 
describe the most important regions for ligands and receptors, as 
well as explain and differentiate, in a molecular and energetic level, 
the binding affinity experimentally found for these ligands.
 

MEMBROS DA BANCA:
Presidente - 6345638 - EUDENILSON LINS DE ALBUQUERQUE
Interno - 1352009 - UMBERTO LAINO FULCO
Interno - 1720860 - VANESSA DE PAULA SOARES RACHETTI
Externo ao Programa - 2985070 - JONAS IVAN NOBRE OLIVEIRA
Externo ao Programa - 6346140 - LUCIANO RODRIGUES DA SILVA
Externo à Instituição - JOSE ALZAMIR PEREIRA DA COSTA - UERN
Externo à Instituição - FABIO FERREIRA DE MEDEIROS - UFCG
Notícia cadastrada em: 21/12/2018 08:38
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