Folding Kinetics of Protein Like Heteropolymers

TL;DR

This study uses a lattice model and Monte Carlo simulations to analyze the folding kinetics of protein-like heteropolymers, revealing how sequence and temperature influence folding times and identifying a glass transition.

Contribution

It introduces a method to select sequences with unique native states and explores the relationship between folding, collapse, and glass transition temperatures.

Findings

Folding time shows a broad temperature plateau and diverges at extremes.

Collapse times are sequence-independent and faster than folding times.

Two classes of sequences are identified based on the relation between Tf and Tg.

Abstract

Using a simple three-dimensional lattice copolymer model and Monte Carlo dynamics, we study the collapse and folding of protein-like heteropolymers. The polymers are 27 monomers long and consist of two monomer types. Although these chains are too long for exhaustive enumeration of all conformations, it is possible to enumerate all the maximally compact conformations, which are 3x3x3 cubes. This allows us to select sequences that have a unique global minimum. We then explore the kinetics of collapse and folding and examine what features determine the various rates. The folding time has a plateau over a broad range of temperatures and diverges at both high and low temperatures. The folding time depends on sequence and is related to the amount of energetic frustration in the native state. The collapse times of the chains are sequence independent and are a few orders of magnitude faster than the folding times, indicating a two-phase folding process. Below a certain temperature the chains exhibit glass-like behavior, characterized by a slowing down of time scales and loss of self-averaging behavior. We explicitly define the glass transition temperature (Tg), and by comparing it to the folding temperature (Tf), we find two classes of sequences: good folders with Tf > Tg and non-folders with Tf < Tg.