Research Description |
We are investigating the interactions that (a) dictate the folding of a polypeptide chain in water into the three-dimensional structure of a native protein and (b) determine the reactivity of such a protein molecule (e.g., as an enzyme) with other small and large molecules.
Both experimental and theoretical methods are used in this research. The experimental work involves genetic engineering and hydrodynamic (e.g., sedimentation and viscosity), spectroscopic (Raman, infrared, fluorescence, nuclear magnetic resonance, electron spin resonance, ultraviolet absorption, circular dichroism, and optical rotatory dispersion), immunochemical, and other physicochemical measurements on proteins, synthetic polymers of amino acids, and model compounds. The theoretical work involves statistical mechanical studies of aqueous solutions of amino acids and peptides, and of conformational changes in proteins and polypeptides, and empirical energy calculations to determine the stable conformations of proteins, polypeptides, and enzyme-substrate complexes.
Much of the experimental and theoretical work involves the determination of the pathways of folding of proteins, and the mechanism of action of thrombin on fibrinogen (an important reaction in the blood clotting process). |
Publications |
Liwo, A.; Khalili, M.; Scheraga, H.A. Ab Initio Simulations
of Protein-Folding Pathways by Molecular Dynamics with the United-Residue
Model of Polypeptide Chains. Proc. Natl. Acad. Sci., U.S.A., 2005, 102, 2362.
Oldziej, S.; Czaplewski, C.; Liwo, A.; Chinchio, M.; Nanias, M.; Vila,
J.A.; Khalili, M.; Arnautova, Y.A.; Jagielska, A.; Makowski, M.; Schafroth,
H.D.; Kazmierkiewicz, R.; Ripoll, D.R.; Pillardy, J.; Saunders, J.A.;
Kang, Y.K.; Gibson, K.D.; Scheraga, H.A. Physics-Based Protein-Structure
Prediction Using a Hierarchical Protocol Based on the UNRES Force Field:
Assessment in Two Blind Tests. Proc. Natl. Acad. Sci., U.S.A., 2005, 102, 7547.
Khalili, M.; Liwo, A.; Rakowski, F; Grochowski, P.; Scheraga, H.A. Molecular
Dynamics with the United-Residue Model of Polypeptide Chains. I. Lagrange
Equations of Motion and Tests of Numerical Stability in the Microcanonical
Mode. J. Phys. Chem. B., 2005, 109, 13785.
Khalili, M.; Liwo, A.; Jagielska, A.; Scheraga, H.A. Molecular Dynamics
with the United-Residue Model of Polypeptide Chains. II. Langevin and
Berendsen-bath Dynamics and Tests on Model a-helical
systems. J. Phys. Chem. B, 2005, 109, 13798.
Khalili, M.; Liwo, A.; Scheraga, H.A. Kinetic studies of folding of
the B-domain of Staphylococcal Protein A with Molecular Dynamics and
a United-Residue (UNRES) Model of Polypeptide Chains. J. Mol. Biol., 2006, 355, 536.
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