Related papers: Out-of-equilibrium selection pressure enhances inf…
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…
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…
Background:Typically, proteins perform key biological functions by interacting with each other. As a consequence, predicting which protein pairs interact is a fundamental problem. Experimental methods are slow, expensive, and may be error…
The interaction of fluid membranes with a scaffold, which can be a planar surface or a more complex structure, is intrinsic to a number of systems - from artificial supported bilayers and vesicles to cellular membranes. In principle, these…
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.…
Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with…
Living cells exhibit an important out-of-equilibrium mechanical activity, mainly due to the forces generated by molecular motors. These motor proteins, acting individually or collectively on the cytoskeleton, contribute to the violation of…
Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution…
Stochasticity is both exploited and controlled by cells. Although the intrinsic stochasticity inherent in biochemistry is relatively well understood, cellular variation, or 'noise', is predominantly generated by interactions of the system…
Time-resolved single-molecule biophysical experiments yield data that contain a wealth of dynamic information, in addition to the equilibrium distributions derived from histograms of the time series. In typical force spectroscopic setups…
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…
The 2024 Nobel Prize in Chemistry was awarded in part for protein structure prediction using AlphaFold2, an artificial intelligence/machine learning (AI/ML) model trained on vast amounts of sequence and 3D structure data. AlphaFold2 and…
Models such as AlphaFold2 and OpenFold have transformed protein structure prediction, yet their inner workings remain poorly understood. We present a methodology to systematically evaluate the contribution of individual OpenFold components…
Statistical analysis of alignments of large numbers of protein sequences has revealed "sectors" of collectively coevolving amino acids in several protein families. Here, we show that selection acting on any functional property of a protein,…
Potts statistical models have become a popular and promising way to analyze mutational covariation in protein Multiple Sequence Alignments (MSAs) in order to understand protein structure, function and fitness. But the statistical…
We show that in experimental atomic force microscopy studies of the lifetime distribution of mechanically stressed folded proteins the effects of externally applied fluctuations can not be distinguished from those of internally present…
At what level does selective pressure effectively act? When considering the reproductive dynamics of interacting and mutating agents, it has long been debated whether selection is better understood by focusing on the individual or if…
Protein structure prediction often hinges on multiple sequence alignments (MSAs), which underperform on low-homology and orphan proteins. We introduce PLAME, a lightweight MSA design framework that leverages evolutionary embeddings from…
Multiple sequence alignment (MSA) data play a crucial role in the study of protein mutations, with contact prediction being a notable application. Existing methods are often model-based or algorithmic and typically do not incorporate…
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…