Power Strokes in Molecular Motors: Predictive, Irrelevant, or Somewhere in Between?

For several decades, molecular motor directionality has been rationalized in terms of the free energy of molecular conformations visited before and after the motor takes a step, a so-called power stroke mechanism with analogues in macroscopic engines. Despite theoretical and experimental demonstrations of its flaws, the power stroke language is quite ingrained, and some communities still value power stroke intuition. By building a catalysis-driven motor into simulated numerical experiments, we here systematically report on how directionality responds when the motor is modified accordingly to power stroke intuition.

From high-dimensional committors to reactive insights.

Transition path theory (TPT) offers a powerful formalism for extracting the rate and mechanism of rare dynamical transitions between metastable states. Most applications of TPT either focus on systems with modestly sized state spaces or use collective variables to try to tame the curse of dimensionality. Increasingly, expressive function approximators such as neural networks and tensor networks have shown promise in computing the central object of TPT, the committor function, even in very high-dimensional systems.

Limits on the Precision of Catenane Molecular Motors: Insights from Thermodynamics and Molecular Dynamics Simulations.

Thermodynamic uncertainty relations (TURs) relate precision to the dissipation rate, yet the inequalities can be far from saturation. Indeed, in catenane molecular motor simulations, we record precision far below the TUR limit. We further show that this inefficiency can be anticipated by four physical parameters: the thermodynamic driving force, fuel decomposition rate, coupling between fuel decomposition and motor motion, and rate of undriven motor motion.

Sterically driven current reversal in a molecular motor model.

Simulations can help unravel the complicated ways in which molecular structure determines function. Here, we use molecular simulations to show how slight alterations of a molecular motor's structure can cause the motor's typical dynamical behavior to reverse directions. Inspired by autonomous synthetic catenane motors, we study the molecular dynamics of a minimal motor model, consisting of a shuttling ring that moves along a track containing interspersed binding sites and catalytic sites.

Genomic study of variants: prevalence and allelic heterogeneity in men with spermatogenic failure.

Human spermatogenesis is a highly intricate process that requires the input of thousands of testis-specific genes. Defects in any of them at any stage of the process can have detrimental effects on sperm production and/or viability. In particular, the function of many meiotic proteins encoded by germ cell specific genes is critical for maturation of haploid spermatids and viable spermatozoa, necessary for fertilization, and is also extremely sensitive to even the slightest change in coding DNA.