Banca de DEFESA: JOHN LENON DE SOUZA SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : JOHN LENON DE SOUZA SANTOS
DATE: 28/02/2020
TIME: 09:00
LOCAL: Sala SS1 - DBG
TITLE:

STUDY OF INTERACTIONS ENERGY BETWEEN THE NOCICEPTIN / ORPHANIN FQ RECEPTOR AND TWO COMPOUNDS WITH ANTIDEPRESSIVE ACTION

KEY WORDS:

Depression. NOP. DFT. MFCC. SB-612111. C-35. Antagonists. Energy analysis.

PAGES: 70
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUBÁREA: Biofísica Molecular
SUMMARY:

Depression is a serious disorder common throughout the world and its recurrence is
closely linked to harm in the lives of the individuals who carry it. Its main characteristics,
such as depressed mood, anhedonia, irritability, concentration difficulties, fatigue,
increased or decreased appetite, insomnia or hypersomnia, and cognitive and locomotor
losses, justify its gravity. Current treatments cause many side effects and take a long time
to start producing the therapeutic effect, which supports the need for the development of
new drugs. In the last two decades, several studies have shown that the NOP receptor can
be a valuable therapeutic target in the field of pharmacological therapy. Some
pharmacological tools addressing to NOP have been developed, such as SB-612111 and
compound 35 (C-35). In this sense, the present work aims to evaluate, by means of
computer simulation techniques, using the Functional Density Theory (DFT) and the
Molecular Fractionation Method with Conjugate Covers (MFCC), the energetic
particularities present in the interaction between the NOP receptor and the SB-612111
ligand, as well as between it and the C-35 ligand, which are antagonists. From obtaining
the crystalline structures in the PDB and using the tools inherent to the field of
computational simulation, it was possible to analyze the energetic contributions present
in each complex formed by these binders and the receptor in question. In total 102 (101)
amino acid fragments for SB (C-35) were observed, with most of the most energetically
relevant residues being part of the hydrophobic bonding pocket and the fragments with the most attractive energy are located at a distance of up to 3 Å, in both complexes: NOP- SB (ASP130 > GLN107 > TYR309 > TYR131); NOP-C-35 (ASP130 > GLN107 > ASP110 > ILE127 > TYR131 > GLN280 > TYR309). The results presented and discussed here are of substantial relevance, given that in recent decades, especially in

recent years, there has been intense research and investment in the search for the
development of more effective antidepressants. Therefore, analyses as described here can
help in the advancement of the pharmacological scenario directed to antidepressants,
targeting the NOP receptor.

BANKING MEMBERS:
Presidente - 1352009 - UMBERTO LAINO FULCO
Interna - 1720860 - VANESSA DE PAULA SOARES RACHETTI
Externa à Instituição - YWLLIANE DA SILVA RODRIGUES MEURER - UFRN