| dc.description.abstract | Depression is a serious and common disorder 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 and its antagonism has shown to be a promising strategy
due to the antidepressant effects reported in preclinical and clinical studies. 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 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: NOPSB (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. | |
