S. A. Allison

Bio: S. A. Allison is an academic researcher from University of Washington. The author has contributed to research in topics: Brownian dynamics & Brownian motion. The author has an hindex of 26, co-authored 31 publications receiving 2111 citations. Previous affiliations of S. A. Allison include Georgia State University & University of Houston.

Brownian dynamics simulation of diffusion‐influenced bimolecular reactions

Abstract: A method is developed and tested for extracting diffusion‐controlled rate constants for condensed phase bimolecular reactions from Brownian dynamics trajectory simulations. This method will be useful when highly detailed model systems are employed, such as those required to explore the complicated range of interactions between enzymes and their substrates. The method is verified by comparing with exact analytical results for simple cases of spheres with uniform reactivity subject to various centrosymmetric Coulombic and Oseen slip hydrodynamic interactions. The utility of the method is illustrated for more complicated cases involving anisotropic reactivity and rotational diffusion.

Torsion Dynamics and Depolarization of Fluorescence of Linear Macromolecules I. Theory and Application to DNAt

Abstract: A model consisting of a series of N+ 1 identical rigid rods connected at their ends by torsion springs and undergoing rotational brownian motion about their fixed symmetry axes is proposed as a model for the torsion dynamics of DNA. The fluorescence anisotropy bfbnund flunrophores is expressed in terms of angular correlation functions, the subsequent calculation of which is virtually identical to that recently presented for the dynamic structure factor of tIse RouseuZimm model. Tin complete time course of the fluorescence anisotropy is divided into four zones, (i) initial exponential decay zone, (ii) iotermediate zone, (iii) longest internal mude zone, and (iv) uniform mode zone. Simple approximate expressions for the lluoresccnee anisotropy are derived for the initial exponential decay zone and for the intermediate zone. The mag- nitude of end-effects, due to enhanced amplitudes of motion near the chain ends, in the intermediate zone is investigated botls numerically and analytically, and the domain of validity of the approximate expression pertinent to that zone is de- termined to be 100-fold smaller than previously supposed. The fluorescence anisotropy decay data of Wahl, Paoletti and Le Pecq for ethidium bound to DNA is interpreted in terms of this nsodel. Although relaxations in zones (iii) and (iv) can be ruled out, it is possible to obtain equally good fits to the decay dala either in zone (i) witls parameters pertinent to a rod-length of 86 base-pairs or in zone (ii) with parameters pertinent to a rod-length of I base pair. However, other data, in- cluding the steady-state polarization anisotropy in concentrated sucrose solution, definitely favor the zone (i) fit with a rod-length of 86 base-pairs, thus providing evidence for isolated torsion joints, or inhomogeneities in the torsional rigidity, nf that particular calf-thymus DNA. A comparison of twisting energies compused from the present optimum torsion con- stants with the measured free-energies of supercoil formation is also given.

Point charge distributions and electrostatic steering in enzyme/substrate encounter: Brownian dynamics of modified copper/zinc superoxide dismutases.

Abstract: The electrostatic steering mechanism of bovine erythrocyte Cu/Zn superoxide dismutase (SOD) was investigated through the use of Brownian dynamics. Simulations of enzyme/substrate encounter were carried out on 14 different SOD models defined by simple changes in the enzyme's point charge distribution. The magnitude and ionic strength dependence of reaction rates, rates for collision anywhere on the enzyme surface, and collision efficiency factors were analyzed to elucidate both the general and specific roles for point charges associated with amino acid residues. Collision rates for the general enzyme surface appear to be solely determined by the net charge on the enzyme. At physiological ionic strength this effect is negligible, with only 6% variation in collision rates observed as the net charge ranges from +2e to -10e. With the exception of a few charged residues in the active-site channel of SOD, point charge modifications had modest effects on reaction rates. For a large region within and surrounding the channel, reaction rates increased or decreased by only 10-15% with the addition or subtraction of a protonic unit of charge, respectively. This effect simply disappeared with increasing distance from the active site. More dramatic effects were seen at only three residues: arginine-141, glutamate-131, and lysine-134. Implications for rate enhancement through site-directed mutagenesis are discussed.

Classical Electrostatics in Biology and Chemistry

Abstract: A major revival in the use of classical electrostatics as an approach to the study of charged and polar molecules in aqueous solution has been made possible through the development of fast numerical and computational methods to solve the Poisson-Boltzmann equation for solute molecules that have complex shapes and charge distributions. Graphical visualization of the calculated electrostatic potentials generated by proteins and nucleic acids has revealed insights into the role of electrostatic interactions in a wide range of biological phenomena. Classical electrostatics has also proved to be successful quantitative tool yielding accurate descriptions of electrical potentials, diffusion limited processes, pH-dependent properties of proteins, ionic strength-dependent phenomena, and the solvation free energies of organic molecules.

The Elasticity of a Single Supercoiled DNA Molecule

Abstract: Single linear DNA molecules were bound at multiple sites at one extremity to a treated glass cover slip and at the other to a magnetic bead. The DNA was therefore torsionally constrained. A magnetic field was used to rotate the beads and thus to coil and pull the DNA. The stretching force was determined by analysis of the Brownian fluctuations of the bead. Here, the elastic behavior of individual λ DNA molecules over- and underwound by up to 500 turns was studied. A sharp transition was discovered from a low to a high extension state at a force of ∼0.45 piconewtons for underwound molecules and at a force of ∼3 piconewtons for overwound ones. These transitions, probably reflecting the formation of alternative structures in stretched coiled DNA molecules, might be relevant for DNA transcription and replication.