Non-equilibrium dynamics of active enzymes

Thesis

Observations of behaviour usually associated with micron-scale living systems and self-propelled particles in enzymatic systems have been attributed to their catalytic activity. In light of the conformational changes that accompany the catalytic cycle, the exciting possibility that an enzyme molecule can generate enough mechanical work to overcome the noisy conditions inside a cell is being investigated, due to its implications on biological self-organisation and intracellular transport. To this end, we develop a theoretical framework for studying the effect of catalytic activity on the dynamics of catalysing enzymes.

Using a simple generic model of an asymmetric dumbbell made of two subunits that are coupled through hydrodynamic interactions, we study the effect of conformational fluctuations of modular macromolecules, such as enzymes, on their dynamical properties. We show that thermal fluctuations can lead to an interplay between the internal and external degrees of freedom, with the consequence of a negative fluctuation-induced correction to the overall diffusion coefficient of the asymmetric dumbbell compared to a rigid symmetric object. This result is directly applicable to studying the effect of the catalytic cycle on the diffusion of the model enzyme, by considering the internal fluctuations in the presence of substrate molecules which can bind and unbind to the enzyme.

We investigate the effect of the modular structure and internal fluctuations on the dynamics of the model enzyme in a concentration gradient of its substrate. The model enzyme is shown to have three types of response to the chemical gradient, including a drift velocity that is modified by hydrodynamic interactions between its constituents, and alignment. In addition to the chemically induced alignment, we predict a second alignment mechanism in response to density gradients.

Finally, we study the effect of hydrodynamic coupling of a pair of our model enzymes on their internal dynamics and show that the sign and strength of the coupling depend on their separation and proximity to a symmetry-breaking region.

Authors: Adeleke-Larodo, T

• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English