Optimal Strategy for Stabilizing Protein Folding Intermediates

TL;DR

This paper establishes that linear optimal control strategies for stabilizing protein folding intermediates are of the Bang-Bang type, providing analytical solutions and phase diagrams, with implications for medicine and protein engineering.

Contribution

It proves that optimal stabilization strategies are Bang-Bang controls for linear stabilizer addition, with analytical derivation of switching times and phase diagrams.

Findings

Optimal control for stabilizing protein intermediates is Bang-Bang.

Analytical derivation of optimal switching times.

Phase diagram analysis with respect to key parameters.

Abstract

To manipulate the protein population at certain functional state through chemical stabilizers is crucial for protein-related studies. It not only plays a key role in protein structure analysis and protein folding kinetics, but also affects protein functionality to a large extent and thus has wide applications in medicine, food industry, etc. However, due to concerns about side effects or financial costs of stabilizers, identifying optimal strategies for enhancing protein stability with a minimal amount of stabilizers is of great importance. Here we prove that either for the fixed terminal time (including both finite and infinite cases) or the free one, the optimal control strategy for stabilizing the folding intermediates with a linear strategy for stabilizer addition belongs to the class of Bang-Bang controls. The corresponding optimal switching time is derived analytically, whose phase diagram with respect to several key parameters is explored in detail. The Bang-Bang control will be broken when nonlinear strategies for stabilizer addition are adopted. Our current study on optimal strategies for protein stabilizers not only offers deep insights into the general picture of protein folding kinetics, but also provides valuable theoretical guidance on treatments for protein-related diseases in medicine.