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.com
Volume 10, Issue 8 (Suppl)
J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Structural Biology 2017
September 18-20, 2017
9
th
International Conference on
Structural Biology
September 18-20, 2017 Zurich, Switzerland
A new protocol to investigate conformational population patterns in the enzymatic activity cycle of
proteins using molecular dynamics and normal mode analysis
Luis Paulo B Scott
Federal University of ABC, Brazil
H
uman immunodeficiency virus type-1 protease (HIV-1 PR) is an aspartic protease whose proteolytic activity is essential
for cleaving precursor viral polyproteins into individual proteins implied in viral replication. Once HIV enters within a
host cell, its RNA is transcribed into DNA through reverse transcriptase, integrated and amplified along with the replication
of the host cell's DNA.
Gag
and
gag-pro-pol
genes are transcribed into messenger RNA, translated into
gag
and
gag-pro-pol
precursors proteins in the cytoplasm, and then assembled at the cell surface for budding and formation of the immature viral
particles. In this work, we propose a computational protocol to generate and select HIV protease conformations relevant to its
function using Normal Mode Analysis (NMA). We have considered structures of the apoenzyme, the protein with its substrate
and product and the protein with a drug. This set of structures should reveal large amplitude motions that are critical to the
protease activity cycle as: substrate acquisition; substrate cleavage and product release. The apoenzyme presents an increased
flap conformational diversity compared to the various complexes, predominantly populated with open flap conformations,
that can possibly be related to the substrates acquisition. The enzyme-substrate complexes show more structural diversity than
enzyme-product complexes, suggesting a role of these conformational changes in catalytic activity. We present a promising
protocol to identify the conformational diversity induced by different types of ligands and that can help the drug design
process.
Biography
Luis Paulo B Scott is an Associate Professor in Federal University of UAFBC. He has his expertise in conformational changes and functional movements of
macromolecules, specially proteins. Over the last four years, his research group has been financed to investigate molecules related to neurodegeneration and
aggregate formation by means of normal mode analysis and molecular dynamics combined. The laboratory coordinated by him has become more and more
specialized in the study of macromolecules structural dynamics (functional movements in collaboration with Dr. David Perahia from France.
luisp37@gmail.comLuis Paulo B Scott, J Proteomics Bioinform 2017, 10:8(Suppl)
DOI: 10.4172/0974-276X-C1-0100