Jack A Tuszyński

Publications of Jack A Tuszyński

• Modeling of relay helix functional dynamics and feasibility of experimental verification by neutron scattering.

  Authors: Miljko V Satarić, Slobodan Zdravković, Jack A Tuszyński

  Chaos (Woodbury, N.Y.). 12/2011; 21(4):043135.

  Cellular long-range transport involves motor proteins (MPs) (especially, kinesin and myosin) which contain a so-called relay helix. Its motion is of crucial importance to the conversion of chemicalCellular long-range transport involves motor proteins (MPs) (especially, kinesin and myosin) which contain a so-called relay helix. Its motion is of crucial importance to the conversion of chemical energy released in ATP hydrolysis into the coordinated mechanical movement of the entire motor protein. In this paper, we propose two combined nonlinear mechanisms for this particular functional activity and suggest the application of neutron scattering assays to experimentally determine the incoherent dynamic structure factor S(q,ω). We argue that this type of experiment is not only feasible but it could offer significant insights into the mechanism of MP function at a molecular level.

• Modeling the effects of drug binding on the dynamic instability of microtubules.

  Authors: Peter Hinow, Vahid Rezania, Manu Lopus, Mary Ann Jordan, Jack A Tuszyński

  Physical biology. 08/2011; 8(5):056004.

  We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady-state microtubules assembled from MAP-free tubulin in the possible presence of aWe propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady-state microtubules assembled from MAP-free tubulin in the possible presence of a microtubule-associated drug. As an example of the latter, we both experimentally and theoretically study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. Our model predicts that among the drugs that act locally at the microtubule tip, primary inhibition of the loss of GDP tubulin results in stronger damping of microtubule dynamics than inhibition of GTP tubulin addition. On the other hand, drugs whose action occurs in the interior of the microtubule need to be present in much higher concentrations to have visible effects.

• Continuous model for microtubule dynamics with catastrophe, rescue, and nucleation processes.

  Authors: Peter Hinow, Vahid Rezania, Jack A Tuszyński

  Physical review. E, Statistical, nonlinear, and soft matter physics. 09/2009; 80(3 Pt 1):031904.

  Microtubules are a major component of the cytoskeleton distinguished by highly dynamic behavior both in vitro and in vivo referred to as dynamic instability. We propose a general mathematical modelMicrotubules are a major component of the cytoskeleton distinguished by highly dynamic behavior both in vitro and in vivo referred to as dynamic instability. We propose a general mathematical model that accounts for the growth, catastrophe, rescue, and nucleation processes in the polymerization of microtubules from tubulin dimers. Our model is an extension of various mathematical models developed earlier formulated in order to capture and unify the various aspects of tubulin polymerization. While attempting to use a minimal number of adjustable parameters, the proposed model covers a broad range of behaviors and has predictive features discussed in the paper. We have analyzed the range of resultant dynamical behavior of the microtubules by changing each of the parameter values at a time and observing the emergence of various dynamical regimes that agree well with the previously reported experimental data and behavior.

• Fractal michaelis-menten kinetics under steady state conditions: Application to mibefradil.

  Authors: Rebeccah E Marsh, Jack A Tuszyński

  Pharmaceutical research. 01/2007; 23(12):2760-7.

  PURPOSE: To provide the first application of fractal kinetics under steady state conditions to pharmacokinetics as a model for the enzymatic elimination of a drug from the body. MATERIALS ANDPURPOSE: To provide the first application of fractal kinetics under steady state conditions to pharmacokinetics as a model for the enzymatic elimination of a drug from the body. MATERIALS AND METHODS: A one-compartment model following fractal Michaelis-Menten kinetics under a steady state is developed and applied to concentration-time data for the cardiac drug mibefradil in dogs. The model predicts a fractal reaction order and a power law asymptotic time-dependence of the drug concentration, therefore a mathematical relationship between the fractal reaction order and the power law exponent is derived. The goodness-of-fit of the model is assessed and compared to that of four other models suggested in the literature. RESULTS: The proposed model provided the best fit to the data. In addition, it correctly predicted the power law shape of the tail of the concentration-time curve. CONCLUSION: A simple one-compartment model with steady state fractal Michaelis-Menten kinetics describing drug elimination from the body most accurately describes the pharmacokinetics of mibefradil in dogs. The new fractal reaction order can be explained in terms of the complex geometry of the liver, the organ responsible for eliminating the drug.

• Complex movements of motor protein relay helices during the power stroke.

  Authors: Miljko V Satarić, Leif Matsson, Jack A Tuszyński

  Physical review. E, Statistical, nonlinear, and soft matter physics. 12/2006; 74(5 Pt 1):051902.

  We use the Toda soliton formalism to propose a possible complex movement of alpha helices with a very important role in energy transduction during the power stroke of motor proteins. We find thatWe use the Toda soliton formalism to propose a possible complex movement of alpha helices with a very important role in energy transduction during the power stroke of motor proteins. We find that this approach has advantages in comparison with the Davydov soliton model and its variants. We estimated the model's parameters and calculated corresponding properties of the predicted solitary waves including propagation velocities and energies. The energies are found to be within the expected range.