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DYNAMICS of BIOMOLECULES |
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We
are focusing on 3 projects: Project
1:
(Quantum Mechanics/Molecular Mechanics) The green
fluorescent protein (GFP) is an intrinsically fluorescent protein
extracted
from the jellyfish Aequorea victoria. The GFP chromophore formation and
its
mutants have been extensively studied. However, a precise understanding
of
fluorescence loss is still lacking. Particularly, our aim is to create
GFP
molecules carrying random amino acids insertions and understand the
effect of
these insertions (e.g.by change in excitation and emission)
experimentally and
computationally. (Figure) A computer-based modeling and bench-top
experiments
are combined to understand the fluorescence of GFP. Random octapeptides
are
inserted into individual loops of the GFP. Amino acid sequences and
fluorescence levels of clones from each loop are determined. The effect
of
peptide insertions into the loop regions of GFP are studied
computationally
using quantum mechanics and molecular dynamics calculations. Both
computational
and experimental results show that random peptide insertions change the
excitation and emission intensity of GFP. We showed that the location
of the
peptide insertion affects the fluorescence levels of the GFP. GFP has
several
applications in todays academic and industrial research including
protein
arrays, drug discovery diagnostics, research reagents, biothreat
detection, and
bionanotechnology. Project
2:
(Molecular Dynamics) Structural organization of
native lipids into bilayers is the result of a complex interplay of
polar lipid
head groups’ interaction with each other, interfacial water,
and the
hydrophobic interactions of the lipid acyl chains. Native lipids act
collectively as a structured solvent of transmembrane and peripheral
membrane proteins
and modulate protein function through hydrophobic interactions,
lipidation, and
bulk modulation of membrane viscosity. Since membrane lipid dynamics
regulate
membrane organization and lipid and protein-mediated signal
transduction,
studies on lipid dynamics and organization are at the center of
understanding
membrane function. We performed MD simulations of DiI-C18(3) in the
fluid phase
of a DPPC bilayer. Project 3:
(Coarsed Grain
Simulations) Macromolecules in the human body interact with ligands
(i.e.
drugs, peptides and other proteins) on specific sites, which have been
defined
as receptor sites. The structure of the receptor site determines what
kinds of
ligand molecules may interact with it. Ligands act by associating with
specific
macromolecules in ways that alter their biochemical or biophysical
activity.
The precise understanding of the molecular basis of drug action is a
big
challenge in biophysics. We developed a new computational tool to
understand
the dynamics of molecular complexes and their interaction with ligands.
Read
more ... (PDF)
Figure 1. Molecular Dynamics Simulations of biological systems
References : (Please note that the PDF files provided in this web site are copyrighted documents) Demirel,
M.C. and Lesk, A.M., Phys.
Rev. Lett., Vol. 95, 2005, 208106 Demirel,
M. C., Atilgan, A. R., Jernigan, R. L., Erman, B.
and Bahar, Atilgan,
A.R., Durell, S.R., Jernigan, R.L., Demirel, M. C.,
Keskin, O., and Bahar, Demirel
M. C., Jernigan,
R. L., Demirel, M. C., and Bahar, Demirel,
M. C., "Equilibrium Dynamics of Folded Proteins,"
M.S. Thesis, Bahar,
Cetinkaya, M..,
Zeytun, A., Sofo,
J.,
Demirel, M.C., How do insertions affect Green Fluorescent Protein,
Chemical
Physics Letters, 2006: 419, 48-54.
Samuel,
B., Demirel, M.C., Haque, A.M., “High resolution
deformation and damage detection using fluorescent dyes”,
JOURNAL OF
MICROMECHANICS AND MICROENGINEERING, Vol. 17, pg 2324–2327,
2007 Gullapalli,
R., Demirel, M.C., Butler P.J. ” Molecular
dynamics simulation of long-chain carbocyanine dyes in a DPPC lipid
bilayer”,
PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Vol. 10, pg 1-13, 2008
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