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Stuart A. Allison Professor, Biophysical Chemistry Ph.D., University of Washington, (1980) Dr. Stuart Allison Department of Chemistry Georgia State University P.O. Box 4098 Atlanta, Georgia 30302-4098
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A problem that has been of primary interest in my lab over
the last few years has involved dynamical modeling studies of
DNA fragments in the size range of 100-1000 base pairs. This
flexibility plays an important role in biological function. It
is of crucial importance in gene recognition, for example,
since almost every protein-DNA complex whose crystallographic
structure has been determined reveals significant changes in
the twist and/or bending of the DNA helix at the binding site.
Over the last year, simulations of transient electric
birefringence (TEB) have been carried out at high electric
fields in an attempt to understand the cause of some unusual
features of actual TEB experiments. One of these is amplitude
inversion where the birefringence of DNA rapidly decays to zero
once the electric field is turned off, then becomes negative,
and finally decays back to zero. From the simulations, we now
know that amplitude inversion is due to deformation of the DNA
into a bow-like configuration (caused by translation of the
charged fragment in a viscous fluid). The rapid return of the
chain to its equilibrium conformation is responsible for
amplitude inversion. Computer intensive modeling is a very
important tool in helping us understand complex physical
phenomenon of this kind. These studies are being extended to
look in detail at the interplay between coil deformation,
electric field strength and pulse duration, molecular weight,
and salt concentration and valency. This work has considerable
relevance to pulsed field electrophoresis, which is of great
practical importance in fractionating DNA's of different
molecular weight.
A closely related computational project has just gotten
underway and involves dynamical simulations of closed circular
DNAs. Formation of a closed DNA ring is often a first step in
DNA folding. The configurations of folded structures are
intimately related to function as is evidenced by the complex
array of enzymes that have evolved to regulate helical winding,
strand separation, and interconversion among topological
isomers such as supercoils, knots, and catenates. Even in
eukaryotes, where chromosomal DNA is linear, DNA frequently
behaves like a closed circle when the ends are constrained to
form a loop around a protein core. The dynamics of circular
chains are undoubtedly influenced by the complex interplay of
"twist" and "writhe" but a realistic dynamical model has only
been developed within the last six months (J.M. Schurr,
University of Washington). Several dynamical models have been
described in the recent literature, but we are convinced that
they are based on either incorrect or unrealistic assumptions
and cannot be taken seriously. In an initial study, we have
looked at the dynamics of 280 bp circular DNA with a linking
number from 0 to -6. Dynamics of chains with linking numbers of
-3 (or lower) are particularly striking. Starting out in a
circle, the chains convert to an interwound (figure-8)
structure with an average lifetime of about 2 microseconds.
Animated movies derived from the dynamical coordinates show
that the transition from circle to interwound is sudden (about
0.2 microseconds), but can take anywhere from 0 to 10
microseconds to occur. Evidently, the circle must pass through
some transition state before converting to a more stable
conformation. During the next year, we shall simulate
fluorescence polarization anisotropy experiments on 200 bp
circular DNA's where experimental anisotropy decay curves are
available.
Representative Publications
"Electrophoresis of Protein Charge Ladders", by S. Allison, J. Carbeck, C. Chen, and F. Burkes, J. Phys. Chem. B., 2004, 108, 4516-4524.
"Electrokinetic Phenomena. Principles and Applications." (Book Review), S. Allison, J. Amer. Chem. Soc., 2004, 126, 6835-6836.
"Analysis of the Electrophoretic Mobility and Viscosity of Dilute Ludox Solutions in Terms of a Spherical Gel Layer Model", S. Allison, J. Colloid and Interface Sci., 2004, 277, 248-254.
"A General Gel Layer Model for the Transport of Colloids and Macroions in Dilute Solution", S. Allison, S. Wall, M. Rasmusson, J. Colloid and Interface Sci., 2003, 263, 84-98.
"The Length Dependence of Translational Diffusion, Free Solution Electrophoretic Mobility, and Electrophoretic Tether Force of Rigid Rod-Like Model Duplex DNA", Allison, S.; Chen, C. Y.; Stigter, D. Biophysical Journal 2001, 81, 2558-2568.
"Boundary Element Modeling of Biomolecular Transport", Allison, S. A. Biophysical Chemistry 2001, 93, 197-213.
"Boundary Element Modeling of the Primary Electroviscous Effect of Dilute Sodium Poly(Styrenesulfonate) in Monovalent Salt Solutions", Chen, C. Y.; Allison, S. Macromolecules 2001, 34, 8397-8398.
"Modeling the Electrophoresis of Short Duplex DNA: Counterions K+ and Tris(+)", Mazur, S.; Chen, C. Y.; Allison, S. A. Journal of Physical Chemistry B 2001, 105, 1100-1108.
"Commentary on the Screened-Oseen, Counterion-Condensation Formalism of Polyion Electrophoresis", Allison, S. A.; Stigter, D. A . Biophysical Journal 2000, 78, 121-124.
"Low Reynolds Number Transport Properties of Axisymmetric Particles Employing Stick and Slip Boundary Conditions", Allison, S. A. Macromolecules 1999, 32, 5304-5312.
"Visualizing Ion Relaxation in the Transport of Short DNA Fragments", Allison, S. A.; Wang, H.; Laue, T. M.; Wilson, T. J.; Wooll, J. O. Biophysical Journal 1999, 76, 2488-2501.
"Modeling the Transport of Charged Biomolecules", Allison, S.; Mazur, S.; Wang, H. Biophys. J., 1999, 76, A54.
"Effect of Regular Anisotropic Permanent Bending on the Diffusional Spinning and Fluorescence Anisotropy of Short DNA Fragments Studied by Brownian Dynamics Simulation", Allison, S .A.; Schurr, J. M. Macromolecules 1997, 30,.7131-7142.
"Modeling the Electrophoresis of Lysozyme .2. Inclusion of Ion Relaxation" Allison, S .A.; Potter, M; Mccammon, J. A. Biophys. J., 1997, 73, 133-140
"Brownian Dynamics Simulation of DNA Fragments in Strong Electric-Fields" Mazur, S.; Allison, S. A. J. Phys. Chem. B.1997, 101, 2244-2250.
"Diffusional Spinning as a Probe of DNA Fragments Conformation - Comment" Schurr, J. M.; Fujimoto, B. S.; Reese, A.; Robinson, B .H. Allison,S. A. J. Phys. Chem. B.1997, 106, 815-816.
"Modeling the Electrophoresis of Rigid Polyions - Inclusion of Ion Relaxation" Allison, S. A. Macromolecules 1996, 29, 7391-7401.
"Comparison of Analytical Theory with Brownian Dynamics
Simulations for Small Linear and Circular DNAs", Heath, P. J.;
Gebe, J. A.; Allison, S. A.; Schurr, J. M.
Macromolecules 1996, 29, 3583-3596.
"A Theory for Electric Dichroism and Birefringence Decays and
Depolarized Dynamic Light-Scattering of Weakly Bending Rods",
Heath, P. J.; Allison, S. A.; Gebe, J. A.; Schurr, J. M.
Macromolecules, 1995, 28, 6600-6607.
"Modeling the Electrophoresis of Rigid Polyions - Application
to Lysozyme", Allison, S. A.; Tran, V. T. Biophys. J.,
1995, 68, 2261-2270.
"Monte-Carlo Simulations of Supercoiling Free-Energies for
Unknotted and Trefoil Knotted DNAs", Gebe, J. A.; Allison, S.
A.; Clendenning, J. B.; Schurr, J. M. Biophys. J.,
1995, 68, 619-633.
"End Effects in Electrostatic Potentials of Cylinders - Models
for DNA Fragments", Allison, S. A. J. Phys. Chem.
1994, 98, 12091-12096.
"Electrophoresis of Spheres by a Discretized Integral-Equation
Finite-Difference Approach", Allison, S.A.; Nambi, P.
Macromolecules, 1994, 27, 1413-1422.
"Effect of Circularization on the Torsion Constant of a Small
DNA", Heath, P. J.; Allison, S. A.; Schurr, J. M. Biophys.
J., 1994, 66, A 156-A 156
"Modeling of Macromolecular Diffusion in Congested Media",
Allison, S. A. Biophys. J., 1993, 65,
1750-1751.
"A Commentary on Gating of the Active Site of Thiose Phosphate
Isomerase - Brownian Dynamics Simulations of Flexible Peptide
Loops in the Enzyme"' Allison, S.A. Biophys. J.,
1993, 64, 1-2.
"Transport of Charged Macromolecules in an Electric Field by a
Numerical Method. 1. Application to a Sphere", Allison, S.A.;
Nambi, P. Macromolecules, 1992, 25,
3971-3978.
"Kinetic Effects of Multiple Charge Modifications in
Enzyme-Substrate Reactions: Brownian Dynamics Simulations of
Cu, Zn Superoxide Dismutase", Sines, J. J.; McCammon, J. A.;
Allison, S. A. J. Comp. Chem., 1992, 13:,
66-69.
"Transport of Polyions in Electric-Fields", Allison, S. A.;
Nambi, P. Faseb J., 1992, 6, A, 175
175.
"Electric Dichroism and Birefringence Decay of Short DNA
Restriction Fragments Studied by Brownian Dynamics Simulation",
Allison, S. A.; Nambi, P. Macromolecules, 1992,
25, 759-768.
"Kinetic Effects of Multiple Charge Modifications in
Enzyme-Substrate Reactions - Brownian Dynamics Simulations of
Cu, Zn Superoxide-Dismutase", Sines, J. J.; Mccammon, J. A.;
Allison, S. A. J. Comp. Chem. 1992, 13
66-69.