Search

Though the biological function of many natural molecular motors is fairly well established, many structure-function details responsible for motor performance remain vague or unknown completely. Recently, we have undertaken a new bottom-up approach to understanding biological molecular motors by designing and building an artificial, protein-based molecular motor dubbed the Tumbleweed (TW). The TW is a purely diffusive motor construct consisting of three DNA-binding proteins attached to a designed, protein-based central hub, where directional stepping along a DNA track is maintained by a temporally periodic external chemical supply. To better understand important design and performance characteristics of the TW, coarse-grained Langevin Dynamics (LD) simulations and numerical solutions to the Master Equation (ME) were carried out. The LD approach, which is a single motor simulation, is particularly suitable for exploring the diffusional behavior of the system, where the ME approach, which models an ensemble of motor states, is best suited for statistically exploring the parameter space of the system and the interaction of processes at different time scales. We present results from these two theoretical approaches that illuminate not only important design and experimental considerations, such as motor geometry and track spacing, but also produce unexpected diffusional behavior. Of particular interest is that the addition of certain internal symmetric potentials can increase motor performance. For example, the addition of a non-specific binding potential, symmetric about the DNA track, can double motor speed by replacing some of the 3D diffusional search by a relatively fast 1D diffusional slide along the DNA. This, and other symmetric potential inputs that increase motor performance by subtly amplifying asymmetries in the system, are not only fundamentally interesting but also may be applicable to any molecular motor that incorporates a diffusional search in its stepping cycle.

Molecular spiders are synthetic molecular motors featuring multiple legs that each can interact with a substrate through binding and cleavage. Experimental studies suggest the motion of the spider in a matrix is biased towards uncleaved substrates, and that spider properties such as processivity can be altered by changing the binding strength of the legs to substrate [R. Pei et al., J. Amer. Chem. Soc.128, 12693 (2006)]. We investigate the origin of biased motion and molecular motor properties of bipedal spiders using Monte Carlo simulations. Our simulations combine a realistic chemical kinetic model, hand-over-hand (HOH) or inchworm (IW) modes of stepping, and the use of a 1D track. We find that substrate cleavage and spider detachment from the track are both contributing mechanisms to population bias but are not necessary for biased motion on an asymmetric track. We investigate the contributions of stepping mechanism to speed, randomness parameter, processivity, coupling and efficiency, and comment on how these molecular motor properties can be altered by changing experimentally tunable kinetic parameters. We then consider the more general case where steps can occur by any mechanism, subject to steric constraints. We compare these results with the above for bipedal spiders and then simulate quadrupedal spiders to investigate the effect of leg number on motor performance.