Molecular motors are responsible for active transport and organization in the cell, underlying an enormous number of crucial biological processes. Dynein is more complicated in its structure and function than other motors. Recent experiments have found that, unlike other motors, dynein can take different size steps along microtubules depending on load and ATP concentration. We use Monte Carlo simulations to model the molecular motor function of cytoplasmic dynein at the single-molecule level. The theory relates dynein's enzymatic properties to its mechanical force production. Our simulations reproduce the main features of recent single-molecule experiments that found a discrete distribution of dynein step sizes, depending on load and ATP concentration. The model reproduces the large steps found experimentally under high ATP and no load by assuming that the ATP binding affinities at the secondary sites decrease as the number of ATP bound to these sites increases. Additionally, to capture the essential features of the step-size distribution at very low ATP concentration and no load, the ATP hydrolysis of the primary site must be dramatically reduced when none of the secondary sites have ATP bound to them. We make testable predictions that should guide future experiments related to dynein function. molecular motors ͉ theory ͉ simulations M olecular motors are responsible for active transport and organization in the cell, underlying an enormous number of crucial biological processes (1). There are three classes of molecular motors, kinesin, myosin, and dynein. Myosins move along actin filaments, kinesin moves toward the plus end of a microtubule (MT), and dynein moves toward the MT minus end. To understand these motors better, experimental studies of the function of the motors at the single-molecule level have been conducted (2-9), and these quantitative measurements have then been modeled theoretically by using coupled differential rate equations (10-15).Dynein is more complicated than kinesin or myosin. This complexity can be seen experimentally in the step-size distribution. The distribution of step sizes for kinesin and myosin are centered about a single value. For kinesin, the average step size is 8 nm (16), and for myosin-V it is 37 nm (17). Dynein, in contrast, displays four different step sizes (8,16,24, and 32 nm), depending on the load and ATP concentration (18). By ''load'' we mean an external backward force applied to a polystyrene bead by using an optical trap, when a dynein molecule is attached to the bead and hauls it along a microtubule. If there is no load, at low ATP the dynein moves with a mixture of 24-and 32-nm steps (18). When load is present, if sufficient ATP is available, the dynein can decrease its step size to 8 nm and produce force up to 1.1 pN. If the load is large enough so that the motor is no longer able to move the bead, we refer to the load as the stalling force. The stalling force increases linearly with ATP concentration before saturating at 1.1 pN (18). In this work, we use Monte...

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Monte Carlo simulation of charge transport is employed to test the suitability of extensively used empirical equations, proposed by Gaussian disorder model (GDM)/ correlated disorder model (CDM), for extracting disorder parameters from the field and temperature dependence of mobility in inhomogeneous organic thin films. Numerous observations suggests that the effective energetic disorder seen by the carrier in an inhomogeneous system decreases with increase in concentration of low disordered regions. However, the conventional analysis of field and temperature dependence of mobility obtained for such system, even with high concentration of low disordered regions, using the empirical equation provides the value of energetic disorder that is close to the value for regions of high disorder in the system rather than the effective energetic disorder. The study also shows that the inaccurate value of energetic disorder extracted using empirical equation in turn affect the extraction of positional disorder parameter. Possible reason for inaccurate estimation of disorder parameters is discussed. We conclude that a modified approach is indispensible to obtain effective disorder parameters for an inhomogeneous system.

The influence of ordered regions (micro crystallites and aggregates) in the other wise disordered polymer host matrix on field and temperature dependence of mobility (μ) has been simulated.Increase in concentration of ordered regions leads to increase in magnitude of mobility and in high field regime the saturation of the mobility occurs at lower electric field strength. The influence of different mean and standard deviation of Gaussian density of states (DOS) of ordered regions on the field dependence of mobility was studied and found to be significant only at higher concentrations. Weak influence of these parameters at low concentrations are attributed to the strong interface effects due to the difference in the standard deviation of DOS of two regions (host and ordered region) and shallow trapping effect by ordered regions. For all the parameters of ordered regions under investigation the temperature dependence of mobility (logμ) and the slope of logμ Vs E 1/2 plot show 1/T 2 dependence.

Monte Carlo simulation was carried out to understand the influence of morphological inhomogeneity on carrier diffusion in organic thin films. The morphological inhomogeneity was considered in the simulation by incorporating the regions of low energetic disorder in a host lattice of high energetic disorder which decreases the overall energetic disorder of the system.For the homogeneous films, the carrier diffusion was found to decrease upon decreasing the energetic disorder. In contrast to this, in the case of inhomogeneous films the carrier diffusion enhanced upon decreasing the overall energetic disorder, up to an optimum value and beyond which the carrier diffusion decreased. Through our simulation, we observed that the behavior of carrier diffusion in the inhomogeneous case is due to the morphology dependent carrier spreading, which acts in addition to the thermal and non-thermal field assisted diffusion mechanisms. This morphological dependence of carrier spreading arises due to the generation of packets of carriers with different jump rates, which is after effect of slow relaxation of the carriers generated in the less disordered regions of inhomogeneous system. Our simulation of morphology dependent carrier spreading and its influence on the basic diffusion process provide deeper insight into the charge transport mechanisms in organic thin films.