Coarse-grained structural modeling of molecular motors
- Molecular motors perform central functions in fundamental biological processes, including cell division, DNA replication, muscle contraction, and intracellular transport. Experimental and computational approaches are needed to uncover the mechanisms by which molecular motors convert chemical energy into mechanical work. A software system called Protein Mechanica has been developed to generate structurally realistic models of molecular motor conformations compatible with experimental data from different sources. It facilitates the construction of models of protein geometry from atomic resolution structures, lower-resolution electron microscopy data and parametric solids. Coarse-grained models of molecular structures are constructed by combining groups of atoms into a system of rigid bodies connected by joints. Contacts between rigid bodies enforce excluded volume constraints, and spring potentials model system elasticity. This simplified representation allows the conformations of complex molecular motors to be simulated interactively, providing a tool for hypothesis building and quantitative comparisons between models and experiments. Protein Mechanica was used to build an atomic-resolution model of a mouse brain myosin V, a dimeric cellular transport motor, in pre- and post powerstroke conformations from partial X-ray crystal structures. A mechanical analysis of the head-neck region model was performed using normal mode analyses and molecular dynamics simulations to guide the construction of a coarse-grained models. The coarse-grained model of myosin V enabled examination of its conformations bound to its actin track. Elastic strain energies calculated from simulations are compatible with observations of single myosin V motors traversing suspended actin filaments that infer that the motor uses a combination of 11 subunit and 13 subunit stride sizes. These calculations extend previous simple mechanical models for step size selection and processivity, and provide atomically detailed models for comparison with future experiments. The Protein Mechanica software described in this dissertation provides a new tool for structural modeling of many different molecular machines, basic understanding and engineering design.
|Type of resource
|electronic; electronic resource; remote
|1 online resource.
|Parker, David William
|Stanford University, Department of Mechanical Engineering
|Bryant, Zev David
|Bryant, Zev David
|Statement of responsibility
|David William Parker.
|Submitted to the Department of Mechanical Engineering.
|Thesis (Ph.D.)--Stanford University, 2011.
- © 2011 by David William Parker
- This work is licensed under a Creative Commons Attribution 3.0 Unported license (CC BY).
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