Frustration, dynamics and catalysis

TL;DR

This paper reviews how local frustration in proteins influences their dynamics and catalytic efficiency, highlighting the interplay between energy landscapes, thermal fluctuations, and evolutionary tuning of protein sequences.

Contribution

It synthesizes recent advances across protein science fields, emphasizing the role of local frustration in enzyme catalysis and protein dynamics.

Findings

Local frustration relates to energy landscape asperities.

Protein evolution modulates local frustration for optimal function.

Dynamics are guided by thermal fluctuations influenced by frustration.

Abstract

The controlled dissipation of chemical potentials is the fundamental way cells make a living. Enzyme-mediated catalysis allows the various transformations to proceed at biologically relevant rates with remarkable precision and efficiency. Theory, experiments and computational studies coincide to show that local frustration is a useful concept to relate protein dynamics with catalytic power. Local frustration gives rise to the asperities of the energy landscapes that can harness the thermal fluctuations to guide the functional protein motions. We review here recent advances into these relationships from various fields of protein science. The biologically relevant dynamics is tuned by the evolution of protein sequences that modulate the local frustration patterns to near optimal values.