Related papers: Inferring repeat protein energetics from evolution…
Proteins contain a large fraction of regular, repeating conformations, called secondary structure. A simple, generic definition of secondary structure is presented which consists of measuring local correlations along the protein chain.…
One of the most puzzling and unsolved challenges in molecular biology is understanding how proteins fold. Despite having advanced predictive tools that can accurately estimate the native structures of proteins, we still lack a comprehensive…
We show that a protein can be trained to recognise multiple conformations, analogous to an associative memory, and provide capacity calculations based on energy fluctuations and information theory. Unlike the linear capacity of a Hopfield…
We study the coupled dynamics of primary and secondary structure formation (i.e. slow genetic sequence selection and fast folding) in the context of a solvable microscopic model that includes both short-range steric forces and and…
We propose a protein model based on a hierarchy of constraints that force the protein to follow certain pathways when changing conformation. The model exhibits a first order phase transition, cooperativity and is exactly solvable. It also…
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…
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…
Protein folding and evolution are intimately linked phenomena. Here, we revisit the concept of exons as potential protein folding modules across 38 abundant and conserved protein families. Taking advantage of genomic exon-intron…
The prediction of the three-dimensional native structure of proteins from the knowledge of their amino acid sequence, known as the protein folding problem, is one of the most important yet unsolved issues of modern science. Since the…
In this work, we discovered a fundamental connection between selection for protein stability and emergence of preferred structures of proteins. Using standard exact 3-dimensional lattice model we evolve sequences starting from random ones…
Protein structures are much more conserved than sequences during evolution. Based on this observation, we investigate the consequences of structural conservation on protein evolution. We study seven of the most studied protein folds,…
Current-day genomes bear the mark of the evolutionary processes. One of the strongest indications is the sequence homology among families of proteins that perform similar biological functions in different species. The number of proteins in…
The structure and function of a protein are determined by its amino acid sequence. While random mutations change a protein's sequence, evolutionary forces shape its structural fold and biological activity. Studies have shown that neutral…
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.…
Proteins encoded by genes containing regions of variable number tandem repeats (VNTRs) are known to be polymorphic within species but the influence of their instability in molecular interactions remains unclear. VNTRs are overrepresented in…
The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…
We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in…
Protein structure prediction and folding are fundamental to understanding biology, with recent deep learning advances reshaping the field. Diffusion-based generative models have revolutionized protein design, enabling the creation of novel…
We study the geometric properties of the energy landscape of coarse-grained, off-lattice models of polymers by endowing the configuration space with a suitable metric, depending on the potential energy function, such that the dynamical…
These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…