Related papers: Direct Coupling Analysis of Epistasis in Allosteri…
The analysis of correlations of amino acid occurrences in globular proteins has led to the development of statistical tools that can identify native contacts -- portions of the chains that come to close distance in folded structural…
In the course of evolution, proteins show a remarkable conservation of their three-dimensional structure and their biological function, leading to strong evolutionary constraints on the sequence variability between homologous proteins. Our…
As a necessary process in drug development, finding a drug compound that can selectively bind to a specific protein is highly challenging and costly. Drug-target affinity (DTA), which represents the strength of drug-target interaction…
The fitness contribution of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations under selection, and can shape the…
We develop a Non-Crossing Approximation (NCA) for the effective cluster problem of the recently developed Dynamical Cluster Approximation (DCA). The DCA technique includes short-ranged correlations by mapping the lattice problem onto a…
Contact-assisted protein folding has made very good progress, but two challenges remain. One is accurate contact prediction for proteins lack of many sequence homologs and the other is that time-consuming folding simulation is often needed…
Canonical Correlation Analysis, CCA, is a widely used multivariate method in omics research for integrating high dimensional datasets. CCA identifies hidden links by deriving linear projections of features maximally correlating datasets.…
Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function impose structural and functional constraints on each residue site. Selective constraints on residue sites are…
Function of proteins or a network of interacting proteins often involves communication between residues that are well separated in sequence. The classic example is the participation of distant residues in allosteric regulation.…
Motivation: Standard algorithms for pairwise protein sequence alignment make the simplifying assumption that amino acid substitutions at neighboring sites are uncorrelated. This assumption allows implementation of fast algorithms for…
Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of…
We introduce a numerical scheme to evolve functional materials that can accomplish a specified mechanical task. In this scheme, the number of solutions, their spatial architectures and the correlations among them can be computed. As an…
Statistical coupling analysis (SCA) is a method for analyzing multiple sequence alignments that was used to identify groups of coevolving residues termed "sectors". The method applies spectral analysis to a matrix obtained by combining…
Learning Ising or Potts models from data has become an important topic in statistical physics and computational biology, with applications to predictions of structural contacts in proteins and other areas of biological data analysis. The…
Proteins are the workhorse molecules of the cell and perform their biological functions by binding to other molecules through physical contact. Protein function is then regulated through coupling of bindings on the protein (allosteric…
Allosteric interactions in DNA are crucial for various biological processes. These interactions are quantified by measuring the change in free energy as a function of the distance between the binding sites for two ligands. Here we show that…
Understanding protein-protein interactions is central to our understanding of almost all complex biological processes. Computational tools exploiting rapidly growing genomic databases to characterize protein-protein interactions are…
Compound-protein pairs dominate FDA-approved drug-target pairs and the prediction of compound-protein affinity and contact (CPAC) could help accelerate drug discovery. In this study we consider proteins as multi-modal data including 1D…
Allostery plays a fundament role in most biological processes. However, little theory is available to describe it outside of two-state models. Here we use a statistical mechanical approach to show that the allosteric coupling between two…
Recombinant Inbred Lines derived from divergent parental lines can display extensive segregation distortion and long-range linkage disequilibrium (LD) between distant loci. These genomic signatures are consistent with epistatic selection…