相关论文: Modeling and prediction of mutation fitness on pro…

Empirical substitution matrices represent the average tendencies of substitutions over various protein families by sacrificing gene-level resolution. We develop a codon-based model, in which mutational tendencies of codon, a genetic code,…

Epigenetic histone modifications play an important role in the maintenance of different cell phenotypes. The exact molecular mechanism for inheritance of the modification patterns over cell generations remains elusive. We construct a…

The evolutionary trajectory of a protein through sequence space is constrained by function and three-dimensional (3D) structure. Residues in spatial proximity tend to co-evolve, yet attempts to invert the evolutionary record to identify…

Evolutionary models measure the probability of amino acid substitutions occurring over different evolutionary distances. We examine various evolutionary models based on empirically derived amino acid substitution matrices. The models are…

MOTIVATION: Proteins fold into complex structures that are crucial for their biological functions. Experimental determination of protein structures is costly and therefore limited to a small fraction of all known proteins. Hence, different…

Motivation: Site directed mutagenesis is widely used to understand the structure and function of biomolecules. Computational prediction of protein mutation impacts offers a fast, economical and potentially accurate alternative to laboratory…

The inverse Potts problem for estimating evolutionary single-site fields and pairwise couplings in homologous protein sequences from their single-site and pairwise amino acid frequencies observed in their multiple sequence alignment would…

We present a sequence-based probabilistic formalism that directly addresses co-operative effects in networks of interacting positions in proteins, providing significantly improved contact prediction, as well as accurate quantitative…

Studying evolutionary correlations in alignments of homologous sequences by means of an inverse Potts model has proven useful to obtain residue-residue contact energies and to predict contacts in proteins. The quality of the results depend…

Stability is a key ingredient of protein fitness and its modification through targeted mutations has applications in various fields such as protein engineering, drug design and deleterious variant interpretation. Many studies have been…

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level…

This paper presents a novel approach for predicting the relative populations of protein conformations using AlphaFold 2, an AI-powered method that has revolutionized biology by enabling the accurate prediction of protein structures. While…

Predicting the effect of mutations in proteins is one of the most critical challenges in protein engineering; by knowing the effect a substitution of one (or several) residues in the protein's sequence has on its overall properties, could…

Protein-protein bindings play a key role in a variety of fundamental biological processes, and thus predicting the effects of amino acid mutations on protein-protein binding is crucial. To tackle the scarcity of annotated mutation data,…

Stabilizing proteins is a foundational step in protein engineering. However, the evolutionary pressure of all extant proteins makes identifying the scarce number of mutations that will improve thermodynamic stability challenging. Deep…

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…

Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. While high-throughput methods have produced large numbers of sequence-function pairs, functional assays do not distinguish…

Accurately determining a change in protein binding affinity upon mutations is important for the discovery and design of novel therapeutics and to assist mutagenesis studies. Determination of change in binding affinity upon mutations…

Protein mutations can have profound effects on biological function, making accurate prediction of property changes critical for drug discovery, protein engineering, and precision medicine. Current approaches rely on fine-tuning…

In this study, the distributions of protein structure classes (or folding types) of experimentally determined structures from a legacy dataset and a comprehensive database (SCOP) are modeled precisely with geometric constructs such as…