Mechanistic rules for de novo design of enzymes

Abstract

Enzymes are nano-scale machines that have evolved to drive chemical reactions out of equilibrium in the right place at the right time. Given the complexity and specificity of enzymatic function, bottom-up design of enzymes presents a daunting task that is far more challenging than making passive molecules with specific binding affinities or building nano-scale mechanically active devices. We present a thermodynamically-consistent model for the operation of such a fuelled enzyme, which uses the energy from a favourable reaction to undergo non-equilibrium conformational changes that in turn catalyze a chemical reaction on an attached substrate molecule. We show that enzymatic function can emerge through a bifurcation upon appropriate implementation of momentum conservation on the effective reaction coordinates of the low dimensional description of the enzyme, and thanks to a generically present dissipative coupling. Our results can complement the recently developed strategies for de novo enzyme design based on machine learning approaches.

References in corpus (10)

• Mechanical Response of a Small Swimmer Driven by Conformational Transitions
• Enhanced diffusion and chemotaxis at the nanoscale
• Sustained unidirectional rotation of a self-organized DNA rotor on a nanopore
• A DNA turbine powered by a transmembrane potential across a nanopore
• Self-organization of primitive metabolic cycles due to non-reciprocal interactions
• Escaping kinetic traps using non-reciprocal interactions
• Entropy production and thermodynamic inference for stochastic microswimmers
• Collective synchronization of dissipatively-coupled noise-activated processes
• Impact of non-reciprocal interactions on colloidal self-assembly with tunable anisotropy
• Nonlinear response theory of molecular machines

Cited by in corpus (2)

• Mechanical inhibition of dissipation in a thermodynamically consistent active solid
• Dumbbell dimer dynamics in three-dimensional chiral fluids