Related papers: Thermodynamic Prediction of Protein Neutrality

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Naturally evolving proteins gradually accumulate mutations while continuing to fold to thermodynamically stable native structures. This process of neutral protein evolution is an important mode of genetic change, and forms the basis for the…

As an example of topic where biology and physics meet, we present the issue of protein folding and stability, and the development of thermodynamics-based bioinformatics tools that predict the stability and thermal resistance of proteins and…

Inverse folding models have proven to be highly effective zero-shot predictors of protein stability. Despite this success, the link between the amino acid preferences of an inverse folding model and the free-energy considerations underlying…

Pre-trained protein language models have demonstrated significant applicability in different protein engineering task. A general usage of these pre-trained transformer models latent representation is to use a mean pool across residue…

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We…

The aim of this work is to elucidate how physical principles of protein design are reflected in natural sequences that evolved in response to the thermal conditions of the environment. Using an exactly solvable lattice model, we design…

Modern biomedicine is challenged to predict the effects of genetic variation. Systematic functional assays of point mutants of proteins have provided valuable empirical information, but vast regions of sequence space remain unexplored.…

A general theoretical framework is developed using free energy functional methods to understand the effects of heterogeneity in the folding of a well-designed protein. Native energetic heterogeneity arising from non-uniformity in native…

Protein structures in nature often exhibit a high degree of regularity (secondary structures, tertiary symmetries, etc.) absent in random compact conformations. We demonstrate in a simple lattice model of protein folding that structural…

For several decades, experimental and computational studies have been used to investigate the potential functional role of knots in protein structures. A property that has attracted considerable attention is thermal stability, i.e., the…

Protein aggregation in cell membrane is vital for the majority of biological functions. Recent experimental results suggest that transmembrane domains of proteins such as $\alpha$-helices and $\beta$-sheets have different structural…

The process of protein folding from an unfolded state to a biologically active, folded conformation is governed by many parameters e.g the sequence of amino acids, intermolecular interactions, the solvent, temperature and chaperon…

Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…

We present a statistical mechanics treatment of the stability of globular proteins which takes explicitly into account the coupling between the protein and water degrees of freedom. This allows us to describe both the cold and the warm…

In this work we employ various methods of analysis (unfolding simulations and comparative analysis of structures and sequences of proteomes of thermophilic organisms) to show that organisms can follow two major strategies of thermophilic…

Predicting protein stability changes induced by single-point mutations has been a persistent challenge over the years, attracting immense interest from numerous researchers. The ability to precisely predict protein thermostability is…

We present a statistical mechanics approach to the protein folding problem. We first review some of the basic properties of proteins, and introduce some physical models to describe their thermodynamics. These models rely on a random…

Normal mode analysis is a widely used technique for reconstructing conformational changes of proteins from the knowledge of native structures. In this Letter, we investigate to what extent normal modes capture the salient features of the…

We report here a new entropic mechanism of protein thermostability due to residual dynamics of rotamer isomerization in native state. All-atom simulations show that Lysines have much greater number of accessible rotamers than Arginines in…