50 Years of Lifson-Roig Models: Application to Molecular Simulation Data

Area of Science:

• Biophysics
• Computational Biology
• Polymer Science

Background:

• Helix-coil transition theories are vital for studying polypeptide folding.
• Lifson-Roig theory is widely used for analyzing experimental and computational data.
• Existing models face challenges in accurately interpreting complex folding behaviors.

Purpose of the Study:

• To investigate issues with Lifson-Roig theory application in helix-coil transitions.
• To analyze the complex phase diagram of a model peptide's folding.
• To propose a more interpretable variant of the Lifson-Roig model.

Main Methods:

• Computer simulations generated folding ensembles for an alanine-rich peptide.
• Analysis employed distinct helicity descriptors and examined backbone angle rigidity.
• A modified Lifson-Roig model was designed to improve parameter interpretability.

Main Results:

• Complex phase diagrams emerged, challenging standard interpretations of nucleation and propagation parameters.
• Fitted parameters showed inconsistencies with residue distributions in helical states.
• Van't Hoff analysis of simple helicity measures provided more robust enthalpy determination.

Conclusions:

• Standard Lifson-Roig models may oversimplify complex helix-coil transitions.
• A modified model offers improved physical interpretability for parameters.
• Results impact the application of these theories to both in silico and in vitro studies.