Information flow, Gating, and Energetics in dimeric molecular motors

Abstract

Molecular motors belonging to the kinesin and myosin super family hydrolyze ATP by cycling through a sequence of chemical states. These cytoplasmic motors are dimers made up of two linked identical monomeric globular proteins. Fueled by the free energy generated by ATP hydrolysis, the motors walk on polar tracks (microtubule or filamentous actin) processively, which means that only one head detaches and executes a mechanical step while the other stays bound to the track. Thus, the one motor head must regulate chemical state of the other, referred to as "gating", a concept that is not fully understood. Inspired by experiments, showing that only a fraction of the energy from ATP hydrolysis is used to advance the kinesin motors against load, we demonstrate that additional energy is used for coordinating the chemical cycles of the two heads in the dimer - a feature that characterizes gating. To this end, we develop a general framework based on information theory and stochastic thermodynamics, and establish that gating could be quantified in terms of information flow between the motor heads. Applications of the theory to kinesin-1 and Myosin V show that information flow occurs, with positive cooperativity, at external resistive loads that are less than a critical value, Fc. When force exceeds Fc, effective information flow ceases. Interestingly, Fc, which is independent of the input energy generated through ATP hydrolysis, coincides with force at which the probability of backward steps starts to increase. Our findings suggest that transport efficiency is optimal only at forces less than Fc, which implies that these motors must operate at low loads under in vivo conditions.

Using Catalysis to Drive Chemistry Away from Equilibrium: Relating Kinetic Asymmetry, Power Strokes, and the Curtin–Hammett Principle in Brownian Ratchets

“…80 In the particular case of processive biological motors such as kinesin, a third viewpoint on the role of information that focuses on the correlation between the two heads was recently proposed. 40 We find these kind of connections between three somewhat disparate disciplines such as synthetic chemistry, theoretical physics, and molecular biology particularly relevant and worth mentioning, not only because connecting fields of knowledge is a good thing to do per se but also because aiding the translation of concepts and relationships between different frameworks fosters a deeper and more interdisciplinary understanding of a system, which can lead to unintuitive connections and breakthroughs.…”

“…We now turn our attention to the relevance of kinetic resolutions to biological molecular motors, as illustrated with a simple, yet paradigmatic, model of a kinesin walker. ,,,, The model uses experimental evidence and considers kinesin to be composed of two “heads” attached to a cargo that walk along a microtubule through a “hand-over-hand” mechanism. ,− The two heads are assumed to be identical but distinguishable, and only states where at least one head is attached to the microtubule are considered. A head is always attached to the microtubule, except when it binds ADP.…”

“…We then propose a solution to the debate on the role of power strokes in Brownian ratchets by showing the circumstances under which the variation of power strokes can (like other conformational changes) affect kinetic asymmetry. We conclude by discussing the role of another theoretical concept, namely, information, which is often used with different meanings in the literature of Brownian ratchets. ,,,, …”

Information thermodynamics for deterministic chemical reaction networks

“…[30][31][32][33] Linear stochastic models of biochemical machines comprising unimolecular or pseudo-unimolecular reactions have been extensively studied from this perspective, revealing the fundamental role of information flows between different degrees of freedom in powering such single molecule machines. [34][35][36][37][38][39] However, chemical engines may, in general, comprise nonlinear processes, such as bimolecular reactions, and are sometimes (almost always in the case of synthetic ones) better described by deterministic dynamics expressed in terms of kinetic equations evolving experimentally measurable concentrations rather than probabilities. At present, a theoretical framework…”

Information Thermodynamics for Deterministic Chemical Reaction Networks

“…Assessing the thermodynamics of bipartite systems requires quantifying energy and information exchanges between the subnetworks by applying the tools of information thermodynamics [30][31][32][33]. Linear stochastic models of biochemical machines comprising unimolecular or pseudounimolecular reactions have been extensively studied from this perspective, revealing the fundamental role of information ows between di erent degrees of freedom in powering such single molecule machines [34][35][36][37][38][39]. However, chemical engines may in general comprise nonlinear processes such as bimolecular reactions and are sometimes (almost always in case of synthetic ones) be er described by deterministic dynamics expressed in terms of kinetic equations evolving experimentally measurable concentrations rather than probabilities.…”