Thermodynamics of Protein Folding from Coarse-Grained Models' Perspectives

TL;DR

This paper reviews how coarse-grained models help understand protein folding, aggregation, and interactions with membranes, emphasizing their ability to classify structural transitions despite finite-size effects.

Contribution

It introduces a mesoscopic modeling approach that simplifies protein behavior analysis, enabling classification of structure formation processes in complex systems.

Findings

Coarse-grained models provide a universal framework for protein folding analysis.

Structural transitions are characterized as pseudophases due to finite-size effects.

External forces influence folding, aggregation, and adsorption processes.

Abstract

Folding and aggregation of proteins, the interaction between proteins and membranes, as well as the adsorption of organic soft matter to inorganic solid substrates belong to the most interesting challenges in understanding structure and function of complex macromolecules. This is reasoned by the interdisciplinary character of the associated questions ranging from the molecular origin of the loss of biological functionality as, for example, in Alzheimer's disease to the development of organic circuits for biosensory applications. In this lecture, we focus on the analysis of mesoscopic models for protein folding, aggregation, and hybrid systems of soft and solid condensed matter. The simplicity of the coarse-grained models allows for a more universal description of the notoriously difficult problem of protein folding. In this approach, classifications of structure formation processes with respect to the conformational pseudophases are possible. This is similar in aggregation and adsorption processes, where the individual folding propensity is influenced by external forces. The main problem in studies of conformational transitions is that the sequences of amino acids proteins are built up of are necessarily of finite length and, therefore, a thermodynamic limit does not exist. Thus, structural transitions are not phase transitions in the strict thermodynamic sense and the analysis of pseudouniversal aspects is intricate, as apparently small-system effects accompany all conformational transitions and cannot be neglected.