Banca de QUALIFICAÇÃO: FELIPE VIEIRA DA FONSECA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : FELIPE VIEIRA DA FONSECA
DATE: 25/11/2019
TIME: 09:00
LOCAL: BioME - PPg-Bioinfo
TITLE:

COMPARISON OF RESIDUE INTERACTION NETWORKS (RINs) TO ASSESS CONFORMATIONAL PROTEIN VARIATION

KEY WORDS:

RINs, Conformational Variation, Mutations, chemical interactions.

PAGES: 55
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Changes in the amino acid sequence may result in alterations in the three-dimensional protein
structure, which may lead to partial or complete loss of function. One way to represent the
chemical interactions between all amino acids in a protein is through the construction of residue
interaction networks (RINs). In RINs, a graph represents the protein 3D structure, with the
nodes as amino acid residues, and the edges as the physicochemical interactions between
amino acids. We hypothesize that the comparison between RINs of the same protein in
different conformations can be used to evaluate the effects of mutations and polymorphisms,
as well as for the analysis and validation of theoretical protein models. Therefore, the present
work aimed to build a tool to compare different RINs for a protein and to use such data to
estimate conformational differences between proteins and also validate models generated by
homology modeling. RINs were created using the RING 2.0 (Residue Interaction Network
Generator) program. The tool developed for this purpose, called Comparator of Residue
Interaction Networks (CoRINs), compares all RIN nodes generated from different structure files
(PDBs) of the same protein, taking into account position, chain and residue, as well as their
interactions with the other amino acids. The tool also presents a plot that estimates the
variation of interactions formed by each residue, which we propose as an estimate for the
conformational alterations of that protein site, from a set of compared PDBs. As a possible
application for this tool, we used a dataset with oncogenes and tumor suppressor genes with
their respective reported mutations mapped according to the connectivity deviation of each
residue. Then we retrieved the different conformations for each resulting protein from a bank
of structural conformers and constructed the RINs using the software RING 2.0 and compared
them with CoRINs. The results show that mutations occurring in the tested oncogenes are
more likely to occur in protein sites with a more significant deviation in the mean number of
chemical interactions. Additionally, most of these genes’ mutations annotated as pathogenic
and associated with clinical cancer cases occurred at sites with the most significant changes
in chemical and physical interactions. These results demonstrate that the CoRINs tool can be
useful in identifying non-covalent interactions essential for protein structure maintenance and
in evolutionary studies, such as in the maintenance of homologous proteins function with high
sequence divergence, as well as for the comparison and validation of theoretical structural
models.

BANKING MEMBERS:
Interno - 1893445 - EUZEBIO GUIMARAES BARBOSA
Interno - 1513597 - JOAO PAULO MATOS SANTOS LIMA
Presidente - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN