Structurally Resolved Coarse-Grained Modeling of Motor Protein Dynamics

Motor proteins are complex macromolecules which have evolved through the biological evolution to carry out a variety of functions related to force generation and intracellular transport. Underlying their organized activity are ordered conformational motions induced by binding of ATP molecules and their hydrolysis. Since these cyclic conformational motions are slow, they cannot be reproduced in molecular-dynamics simulations with all-atom models. Therefore, coarse-grained descriptions of reduced complexity are needed. In this Thesis, a coarse-grained mechanical model, with a protein pictured as a deformable elastic network object, has been employed. The focus was on the investigations of helicase proteins which are molecular motors that translocate in a cell over nucleic acids and unwind their duplex structure. By using the coarse-grained dynamical description for the protein and DNA and including interactions with ATP molecules, we have successfully followed entire operation cycles of the hepatitis C virus (HCV) helicase, for which a large amount of experimental data is available. Thus, the operation of a real molecular motor could be reproduced for the first time in structurally resolved dynamical simulations. Additionally, conformational relaxation dynamics in three other helicases from the same superfamily 2 has been investigated through coarse-grained numerical simulations. In the last chapter of the Thesis, a different, but related problem is addressed. There, we construct and investigate an elastic-network model of a device that can be viewed as a prototype of artificial molecular motors. Similar to myosin motors responsible for force generation in the muscles, the designed machine is able to convert, through a ratchet mechanism, its active cyclic internal motions into a steady net force used to pull a filament. Thermal fluctuations are taken into account and artificial motor operation at different fluctuation levels is discussed.