CPM Seminar

Dynamic Properties of Synthetic Protein Nano-motor Constructs

Martin Zuckermann

Department of Physics
Simon Fraser University & McGill University

Our synthetic motor project is inspired by the properties of biological stepping motors such as kinesin and myosin V. It is aimed determining the design criteria and constructing controllable synthetic protein/DNA nano-scale motors which mimic the properties of biomotors. The project involves four experimental research groups: the Forde Laboratory at SFU, the Linke Laboratory at Lund University, the Woolfson Laboratory at Bristol University and the Curmi Laboratory at the University of New South Wales. My task is to provide guidance for experiments on our present motor constructs and for any future designs for novel motors. To this end, my co-workers and I use numerical simulation and analytic methods such as Langevin dynamics in the over-damped limit, the Gillespie algorithm, the Metropolis Monte Carlo algorithm and the Master Equation formalism. I will discuss the following nano-motor constructs in detail:

1. The Tumbleweed (TW) is a concept for a synthetic, tri-pedal protein-based motor, which is designed to move uni-directionally by a rectified tumbling motion along a dsDNA track. The track is designed in such a way that the ‘feet’ (repressor proteins) can bind when ligands are present in the solution. The directional motion and processivity (the ability of the motor to take many steps before detaching from its track or surface) of the TW is controlled by temporally periodic ligand pulses. To simulate the kinetic properties of the TW, we propose a minimal model for three connected rods in a Y-shape, known as the “Y-motor”. The structure can be either rigid or totally flexible and the ‘feet’, representing three different repressors, can bind to a one-dimensional lattice with appropriate binding sites. Simulation results for the TW with both rigid rods and a more flexible model in which the rods are replaced by water-soluble polypeptide chains will be presented.
2. Our most recent construct, SKAM-2R (from synthetic kinesin analogue motor), is a novel linear motor construct whose design is based on the technology of the TW. However, it behaves in a bipedal manner as it uses only two types of repressor while incorporating a mechanism from the functioning of the bipedal biological motor, kinesin. Our group is very excited about this new construct as it may allow us to find out more information about how kinesin functions and, hopefully, enable us to design an autonomous synthetic protein motor. Our simulations show that SKAM-2R is a stable processive and directional motor, which simply reverses on the application of a sufficiently high rearward force without stalling! I hope to present a version of this motor which exhibits a stall force.
3. Work is also in progress on two other motors, the Molecular Spider (MS) and the Lawnmower (LM). The MS is a soluble, multi-pedal nano-device that diffuses on a two- dimensional surface by enzymatic action (Pei et al. JACS 128 12693 (2006)). The ‘legs’ of the MS are synthetic ssDNA enzymes which can bind to a substrate on the surface. They then cleave the substrate into two products, one of which remains on the surface. The legs of the MS can also bind to the latter product, although the binding is weaker than to the original substrate. Our work on studying the motor properties of the MS has already been published. A new motor construct, the Lawnmower (LM), extends the MS model. It is an analogous nano-device composed of a quantum dot to which several proteases are linked via polypeptide chains. The LM ‘walks’ on a one-dimensional track or a two-dimensional surface containing proteins that can be cleaved by the proteases and its motor properties are thus expected to be similar to those of the MS. The construction of the TW and LM are close to completion and a minimal theoretical model of the LM is ready for numerical simulation.