UNDERSTANDING THE MOTILITY OF MOLECULAR MOTORS USING THEORY AND SIMULATIONS

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dc.contributor.advisorThirumalai, Devarajanen_US
dc.contributor.authorGoldtzvik, Yonathan Yitshaken_US
dc.contributor.departmentBiophysics (BIPH)en_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2018-01-23T06:41:10Z
dc.date.available2018-01-23T06:41:10Z
dc.date.issued2017en_US
dc.description.abstractMolecular motors are indispensable machines that are in charge of transporting cargoes within living cells. Despite recent advances in the study of these molecules, there is much that we still do not understand regarding the underlying mechanisms that allow them to efficiently move cargoes along polar cellular filaments. In this thesis, I report my investigation on two motor proteins superfamilies, dyneins and kinesins. Using theoretical modeling, we provide fundamental insight into their function. Dynein is a large motor that transports cargo along microtubules towards their negative pole. Unlike other motors, such as conventional kinesin, the motility of dynein is highly stochastic. We developed a novel theoretical approach, which reproduces a wide variety of its properties, including the unique step size distribution observed in experiments. Furthermore, our model enables us to derive several simple expressions that can be fitted to experiment, thus providing a physical interpretation. A less understood aspect of dynein is the complex set of allosteric transitions in response to ATP binding and hydrolysis, and microtubule binding. The resulting conformational transitions propel the motor forward to the minus end of the microtubule. Furthermore, its activity is regulated by external strain. Using coarse grained Brownian dynamics simulations, we show that a couple of insert loops in the AAA2, a sub domain in the AAA+ ring in the motor domain, play an important role in several of the alllosteric pathways. Kinesins are highly processive motor proteins that transport cargo along microtubules toward their positive poles. Experiments show that the kinesin motor domains propel the motor forward by passing each other in a hand-over-hand motion. However, there is a debate as to whether the motor domains do so in a symmetrical manner or an asymmetrical motion. Using coarse grained Brownian dynamics simulations of the kinesin dimer, we show that the kinesin stepping mechanism is influenced by the size of its cargo. Furthermore, we find that stepping occurs by a combinations of both the symmetric and asymmetric mechanisms. The results I present in this thesis are a testimony that theoretical approaches are invaluable to the study of molecular motors.en_US
dc.identifierhttps://doi.org/10.13016/M22J68602
dc.identifier.urihttp://hdl.handle.net/1903/20356
dc.language.isoenen_US
dc.subject.pqcontrolledBiophysicsen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledMolecular physicsen_US
dc.subject.pquncontrolledBrownian Dynamics Simulationsen_US
dc.subject.pquncontrolledCoarse Grained Modelsen_US
dc.subject.pquncontrolledDyneinen_US
dc.subject.pquncontrolledKinesinen_US
dc.subject.pquncontrolledMolecular Motorsen_US
dc.subject.pquncontrolledMotor Proteinsen_US
dc.titleUNDERSTANDING THE MOTILITY OF MOLECULAR MOTORS USING THEORY AND SIMULATIONSen_US
dc.typeDissertationen_US

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