Related papers: Stability and the Evolvability of Function in a Mo…
Protein folding models have achieved groundbreaking results typically via a combination of integrating domain knowledge into the architectural blocks and training pipelines. Nonetheless, given the success of generative models across…
Several physical mechanisms have been proposed to explain allostery in proteins. They differ by the number of internal states that they assume a protein to occupy, leaving open the question of what controls the emergence of these distinct…
Only about 1,000 qualitatively different protein folds are believed to exist in nature. Here, we review theoretical studies which suggest that some folds are intrinsically more designable than others, {\it i.e.} are lowest energy states of…
How do living cells achieve sufficient abundances of functional protein complexes while minimizing promiscuous non-functional interactions? Here we study this problem using a first-principle model of the cell whose phenotypic traits are…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
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…
The stability of model proteins with designed sequences is assessed in terms of the number of sequences (obtained from the designed sequence through mutations), which fold into 5the ``native'' conformation. By a complete enumeration of the…
The dynamics of folding of proteins is studied by means of a phenomenological master equation. The energy distribution is taken as a truncated exponential for the misfolded states plus a native state sitting below the continuum. The…
The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated…
The dynamics of a folded protein is studied in water and glycerol at a series of temperatures below and above their respective dynamical transition. The system is modeled in two distinct states whereby the protein is decoupled from the bulk…
We propose a model that explains the hierarchical organization of proteins in fold families. The model, which is based on the evolutionary selection of proteins by their native state stability, reproduces patterns of amino acids conserved…
The binding of a ligand molecule to a protein is often accompanied by conformational changes of the protein. A central question is whether the ligand induces the conformational change (induced-fit), or rather selects and stabilizes a…
Natural protein sequences somehow encode the structural forms that these molecules adopt. Recent developments in structure-prediction are agnostic to the mechanisms by which proteins fold and represent them as static objects. However, the…
Proteins, essential to biological systems, perform functions intricately linked to their three-dimensional structures. Understanding the relationship between protein structures and their amino acid sequences remains a core challenge in…
Enzymes are on the front lines of evolution. All living organisms rely on highly efficient, specific enzymes for growth, sustenance, and reproduction; and many diseases are a consequence of a mutation on an enzyme that affects its catalytic…
Phase separation has emerged as an essential concept for the spatial organization inside biological cells. However, despite the clear relevance to virtually all physiological functions, we understand surprisingly little about what phases…
We review the recent progress in computational approaches to protein design which builds on advances in statistical-mechanical protein folding theory. In particular, we evaluate the degeneracy of the protein code (i.e. how many sequences…
A reduced model, which can fold both helix and sheet structures, is proposed to study the problem of protein folding. The goal of this model is to find an unbiased effective potential that has included the effects of water and at the same…
The paper deals with a nonlinear evolution equation describing the dynamics of a non homogeneous multiply hinged beam, subject to a nonlocal restoring force of displacement type. First, a spectral analysis for the associated weighted…
Much recent work has explored molecular and population-genetic constraints on the rate of protein sequence evolution. The best predictor of evolutionary rate is expression level, for reasons which have remained unexplained. Here, we…