Banca de DEFESA: ANNE CAROLINE LEONIDAS PEREIRA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : ANNE CAROLINE LEONIDAS PEREIRA
DATE: 27/02/2020
TIME: 08:00
LOCAL: sala da física na biofísica
TITLE:

IN SILICO ANALYSIS OF THE INTERACTION BETWEEN HLA-A * 0201 AND MODIFIED MELANOMA PEPTIDES WITH IMMUNOTHERAPIC POTENTIAL

KEY WORDS:

melanoma, immunotherapy, gp100, DFT and MFCC

PAGES: 99
BIG AREA: Ciências Biológicas
AREA: Biofísica
SUBÁREA: Biofísica Molecular
SUMMARY:

Melanoma is a type of skin cancer affects melanocytes increasing incidence worldwide. It is highly lethal and cause metastases. Due to the severity of the disease, conventional formal treatments such as radiotherapy and chemotherapy are not usually effective in the advanced stages of melanoma. Therefore, studies of new therapeutic approaches based on immunotherapy were developed, which have the principle of modulating the immune system against neoplastic cells. However, neoplastic cells can evade anti-tumor immune responses. After to advances in molecular immunology, it has been observed that glycoprotein 100 (gp100), the structural component of melanosome, is over-expressed in melanoma and it causes to trigger T cell activation. However, modifications in peptide sequences in HLA recognition regions, it is possible increase affinity promoting a better immune response. In this sense, this work conducted an ab initio study of the interaction of gp100 modified peptides between HLA-A*0201. For this, we used methods based on quantum mechanics, like the Density Functional Theory (DFT). The peptide-HLA interaction energies were calculated after the partition of the structures by the Conjugated Caps Molecular Fragmentation Method (MFCC). The results showed that the terminal amino acids of the peptides had greater energetic interaction compared to the central amino acids. Peptide C, which replaced one alanine with valine at position 9, was the one with the highest HLA-A*0201 interaction energy and was the only mutation that increased the individual affinity of the residue. Mutations in peptides B, alanine by glutamate at position 3, and C, glycine by alanine at position 5, caused loss of affinity for the receptor. In addition, due to mutations in peptide sequence, conformational changes in peptides impacted the adjacent amino acids energy profile. The main residue-residue interactions were also established for each position of peptide sequences. The main HLA-A*0201 amino acids were: Tyr59, Glu63, Lys66, Asp77, Trp167, Tyr159, Thr143 and Lys146 showing the most energetic interactions with the peptide residues.

BANKING MEMBERS:
Interno - 2411793 - LEONARDO DANTAS MACHADO
Presidente - 1352009 - UMBERTO LAINO FULCO
Externa à Instituição - YWLLIANE DA SILVA RODRIGUES MEURER - UNIFESP