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, I., "Identification of Kinetically Hot Residues in Proteins," PROTEIN SCIENCE, Vol. 7, No. 12, 1998, pp. 2522 -- 2532.

Atilgan, A.R., Durell, S.R., Jernigan, R.L., Demirel, M. C., Keskin, O., and Bahar, I., "Anisotropy of Fluctuation Dynamics of Protein with an Elastic Network Model," BIOPHYSICAL JOURNAL , Vol 80, Issue 1. 2001.  

Demirel M. C., Bahar I., Atilgan A.R., "Predicting the ensemble of unfolding pathways for proteins: An updated incremental Lagrangean model," BIOPHYSICAL JOURNAL Vol. 76, No. 1, 1999, pp. A176.

Jernigan, R. L., Demirel, M. C., and Bahar, I., "Relating Structure to Function through the Dominant Modes of Motion of DNA Topoisomerase II," INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Vol. 75, Special Issue: Biophysics Quarterly: In Memory of Bernard Pullman, 1999, pp. 301 -- 312.

Demirel, M. C., "Equilibrium Dynamics of Folded Proteins," M.S. Thesis, Bogazici University, Institute for Graduate Studies in Science and Engineering, 1998.

Bahar, I., Atilgan, A. R., Demirel, M. C. and Erman, B., "Vibrational Dynamics of Folded Proteins: Significance of Slow and Fast Motions in Relation to Function and Stability," PHYSICAL REVIEW LETTERS, Vol. 80, No. 12, 1998, pp. 2733 -- 2736.

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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Huck Life Science Institute


Materials Research Institute

Our research is supported by:

http://www.psu.edu    http://www.onr.navy.mil    http://icam.ucop.edu/
http://www.avh.de    http://www.jnj.com