Related papers: Capturing coevolutionary signals in repeat protein…
Models of protein energetics which neglect interactions between amino acids that are not adjacent in the native state, such as the Go model, encode or underlie many influential ideas on protein folding. Implicit in this simplification is a…
Correlations between two variables of a high-dimensional system can be indicative of an underlying interaction, but can also result from indirect effects. Inverse Ising inference is a method to distinguish one from the other. Essentially,…
Recent experiments and simulations have demonstrated that proteins can fold on the ribosome. However, the extent and generality of fitness effects resulting from co-translational folding remain open questions. Here we report a genome-wide…
The Predictive Associative Memory (PAM) framework posits that useful relationships often connect items that co-occur in shared contexts rather than items that appear similar in embedding space. A contrastive MLP trained on co-occurrence…
Large multidimensionality of high-throughput datasets pertaining to cell signaling and gene regulation renders it difficult to extract mechanisms underlying the complex kinetics involving various biochemical compounds (e.g., proteins,…
Recombination is a powerful evolutionary process that shapes the genetic diversity observed in the populations of many species. Reconstructing genealogies in the presence of recombination from sequencing data is a very challenging problem,…
Several processes in the cell, such as gene regulation, start when key proteins recognise and bind to short DNA sequences. However, as these sequences can be hundreds of million times shorter than the genome, they are hard to find by simple…
By observing trends in the folding kinetics of experimental 2-state proteins at their transition midpoints, and by observing trends in the barrier heights of numerous simulations of coarse grained, C-alpha model, Go proteins, we show that…
The inverse Potts problem to infer a Boltzmann distribution for homologous protein sequences from their single-site and pairwise amino acid frequencies recently attracts a great deal of attention in the studies of protein structure and…
Complex interactions between genes or proteins contribute a substantial part to phenotypic evolution. Here we develop an evolutionarily grounded method for the cross-species analysis of interaction networks by {\em alignment}, which maps…
Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and…
The mechanisms by which a protein's 3D structure can be determined based on its amino acid sequence have long been one of the key mysteries of biophysics. Often simplistic models, such as those derived from geometric constraints, capture…
Starting from linear chains of amino acids, the spontaneous folding of proteins into their elaborate three-dimensional structures is one of the remarkable examples of biological self-organization. We investigated native state structures of…
Circular permutation connects the N and C termini of a protein and concurrently cleaves elsewhere in the chain, providing an important mechanism for generating novel protein fold and functions. However, their in genomes is unknown because…
Genetic association studies, in particular the genome-wide association study design, have provided a wealth of novel insights into the aetiology of a wide range of human diseases and traits. The next challenge consists of understanding the…
The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or of wider and sometimes highly elaborated motions. Coarse-grained elastic-network descriptions are…
Making use of a simplified model for protein folding, it can be shown that conformations which are particularly stable when their energy is minimized with respect to amino acid sequence (in the sense that they display a large energy gap to…
Automated identification of protein conformational states from simulation of an ensemble of structures is a hard problem because it requires teaching a computer to recognize shapes. We adapt the naive Bayes classifier from the machine…
Motivation: Drug discovery demands rapid quantification of compound-protein interaction (CPI). However, there is a lack of methods that can predict compound-protein affinity from sequences alone with high applicability, accuracy, and…
Local and global inference methods have been developed to infer structural contacts from multiple sequence alignments of homologous proteins. They rely on correlations in amino-acid usage at contacting sites. Because homologous proteins…