Related papers: From evolution to folding of repeat proteins
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…
Designing protein sequences that fold into a target 3-D structure, termed as the inverse folding problem, is central to protein engineering. However, it remains challenging due to the vast sequence space and the importance of local…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
Despite the importance of a thermodynamically stable structure with a conserved fold for protein function, almost all evolutionary models neglect site-site correlations that arise from physical interactions between neighboring amino acid…
Mechanical stretching of secondary structures is studied through molecular dynamics simulations of a Go-like model. Force vs. displacement curves are studied as a function of the stiffness and velocity of the pulling device. The succession…
Proteins exist as a dynamic ensemble of multiple conformations, and these motions are often crucial for their functions. However, current structure prediction methods predominantly yield a single conformation, overlooking the conformational…
Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended timescales. Our methodology involves simulating proteins with molecular…
We propose that protein loops can be interpreted as topological domain-wall solitons. They interpolate between ground states that are the secondary structures like alpha-helices and beta-strands. Entire proteins can then be folded simply by…
In the past years, the folding kinetics of many small single-domain proteins has been characterized by mutational Phi-value analysis. In this article, a simple, essentially parameter-free model is introduced which derives folding routes…
A theoretical analysis of the unfolding pathway of simple modular proteins in length- controlled pulling experiments is put forward. Within this framework, we predict the first module to unfold in a chain of identical units, emphasizing the…
Proteins populate a manifold in the high-dimensional sequence space whose geometrical structure guides their natural evolution. Leveraging recently-developed structure prediction tools based on transformer models, we first examine the…
Computational protein design facilitates discovery of novel proteins with prescribed structure and functionality. Exciting designs were recently reported using novel data-driven methodologies that can be roughly divided into two categories:…
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…
Understanding of the evolutionary origins of protein structures represents a key component of the understanding of molecular evolution as a whole. Here we seek to elucidate how the features of an underlying protein structural "space" might…
The number of protein structures is far less than the number of sequences. By imposing simple generic features of proteins (low energy and compaction) on all possible sequences we show that the structure space is sparse compared to the…
Deep learning has transformed protein design, enabling accurate structure prediction, sequence optimization, and de novo protein generation. Advances in single-chain protein structure prediction via AlphaFold2, RoseTTAFold, ESMFold, and…
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…
A method that reconstructs protein residue networks using suitable node selection and edge recovery policies produced numerical observations that correlate strongly (Pearson's correlation coefficient < -0.83) with published folding rates…
Recent high resolution experiments have provided a quantitative description of the statistical properties of interphase chromatin at large scales. These findings have stimulated a search for generic physical interactions that give rise to…
Proteins, by virtue of their central role in most biological processes, represent one of the key subjects of the study of molecular evolution. Inherent to the indispensability of proteins for living cells is the fact that a given protein…