arXiv subjects

D. Evan Piephoff

Publications and source records attributed to D. Evan Piephoff.

4 recordsLinked to original sources

arXiv2026

First-Passage Time Fluctuation Theorem and Thermodynamic Bound in Cooperative Biomolecular Networks

Using a pathway analysis technique, a dynamic fluctuation relation is derived for a kinetically cooperative biomolecular machine (e.g., an enzyme or a motor protein). This new relation indicates that, in the absence of hidden current, a fluctuation theorem can be established for the first-passage time of the observable process, and we show that this dramatic reduction is a general feature applicable to a wide variety of cooperative networks. This first-passage time fluctuation theorem can be experimentally tested, with its violation serving as a unique signature of hidden detailed balance breaking. Additionally, we obtain a remarkably compact exact expression for the integrated correction to this fluctuation theorem, as well as the general form, revealing a thermodynamic bound on the kinetic branching ratio (i.e., the forward-to-backward observable process probability ratio). These results provide detailed insight into the rich connections between dynamic measurements and the underlying nonequilibrium thermodynamics for cooperative biomolecular machines.

physics.bio-ph↗

arXiv2025

Stochastic Thermodynamics of Cooperative Biomolecular Machines: Fluctuation Relations and Hidden Detailed Balance Breaking

We examine a biomolecular machine involving a driven, observable process coupled to a hidden process in a kinetically cooperative manner. A stochastic thermodynamics framework is employed to analyze a fluctuation theorem for the first-passage time of the observable process under nonequilibrium steady-state conditions. Based on a generic kinetic model, we demonstrate that, along first-passage trajectories, entropy production remains constant when the changes in stochastic entropy and free energy of the machine are balanced, which corresponds to zero net hidden flux through the initial state manifold. Under this condition, which we define quite generally, this first-passage time fluctuation theorem can be established, with its violation serving as an experimentally detectable signature of hidden detailed balance breaking (which we subsequently characterize). In addition, using an enzymatic model, we show that the violation of our first-passage time fluctuation theorem can be thought of as a consequence of the breakdown of local detailed balance in the steps linking coarse-grained states that correspond to the initial and intermediate state manifolds. In the absence of hidden current, the fluctuation theorem is restored, and a mesoscopic local detailed balance condition can be established, which has implications for the thermodynamic analysis of driven, coarse-grained systems. This work sheds significant light on the unique connections between stochastic thermodynamic quantities and kinetic measurements in complex cooperative networks.

cond-mat.stat-mech↗

arXiv2017

Conformational Nonequilibrium Enzyme Kinetics: Generalized Michaelis-Menten Equation

In a conformational nonequilibrium steady state (cNESS), enzyme turnover is modulated by the underlying conformational dynamics. Based on a discrete kinetic network model, we use the integrated probability flux balance method to derive the cNESS turnover rate for a conformation-modulated enzymatic reaction. The traditional Michaelis-Menten (MM) rate equation is extended to a generalized form, which includes non-MM corrections induced by conformational population currents within combined cyclic kinetic loops. When conformational detailed balance is satisfied, the turnover rate reduces to the MM functional form, explaining its validity for many enzymatic systems. For the first time, a one-to-one correspondence is established between non-MM terms and combined cyclic loops with unbalanced conformational currents. Cooperativity resulting from nonequilibrium conformational dynamics has been observed in enzymatic reactions, and we provide a novel, rigorous means of predicting and characterizing such behavior. Our generalized MM equation affords a systematic approach for exploring cNESS enzyme kinetics.

physics.bio-ph↗

arXiv2017

Generic Schemes for Single Molecule Kinetics 2: Information Content of the Poisson Indicator

Recently, we described a pathway analysis technique (paper 1) for analyzing generic schemes for single-molecule kinetics based upon the first-passage time distribution. Here, we employ this method to derive expressions for the Poisson indicator, a measure of stochastic variation (essentially equivalent to the Fano factor and Mandel's Q parameter), for various renewal (memoryless) enzymatic reactions. We examine its dependence on substrate concentration, without assuming all steps follow Poissonian kinetics. Based upon fitting to the functional forms of the first two waiting time moments, we show that, to second order, the non-Poissonian kinetics are generally underdetermined but can be specified in certain scenarios. For an enzymatic reaction with an arbitrary intermediate topology, we identify a generic minimum of the Poisson indicator as a function of substrate concentration, which can be used to tune substrate concentration to the stochastic fluctuations and estimate the largest number of underlying consecutive links in a turnover cycle. We identify a local maximum of the Poisson indicator (with respect to substrate concentration) for a renewal process as a signature of competitive binding, either between a substrate and an inhibitor or between multiple substrates. Our analysis explores the rich connections between Poisson indicator measurements and microscopic kinetic mechanisms.

physics.bio-ph↗