Capillarity-like growth of protein folding nuclei

TL;DR

This study investigates the growth patterns of protein folding nuclei using a capillarity-like model, revealing that the folded core is generally diffuse and growth varies among proteins, supporting a capillarity-based folding mechanism.

Contribution

It introduces a generalized capillarity scaling framework to analyze protein folding nuclei and characterizes their growth patterns and structural diffuseness.

Findings

Average scaling exponent is 0.33, indicating diffuse folded cores.

Three distinct growth patterns of folding nuclei identified.

Quantitative analysis of packing fractions supports capillarity-like growth model.

Abstract

We analyzed folding routes predicted by a variational model in terms of a generalized formalism of the capillarity scaling theory for 28 two-state proteins. The scaling exponent ranged from 0.2 to 0.45 with an average of 0.33. This average value corresponds to packing of rigid objects.That is, on average the folded core of the nucleus is found to be relatively diffuse. We also studied the growth of the folding nucleus and interface along the folding route in terms of the density or packing fraction. The evolution of the folded core and interface regions can be classified into three patterns of growth depending on how the growth of the folded core is balanced by changes in density of the interface. Finally, we quantified the diffuse versus polarized structure of the critical nucleus through direct calculation of the packing fraction of the folded core and interface regions. Our results support the general picture of describing protein folding as the capillarity-like growth of folding nuclei.