相关论文: The Energetics of Molecular Adaptation in Transcri…
Specific binding of proteins to DNA is one of the most common ways in which gene expression is controlled. Although general rules for the DNA-protein recognition can be derived, the ambiguous and complex nature of this mechanism precludes a…
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.…
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…
Natural protein sequences contain a record of their history. A common constraint in a given protein family is the ability to fold to specific structures, and it has been shown possible to infer the main native ensemble by analyzing…
Quantifying the effects of amino acid mutations in proteins presents a significant challenge due to the vast combinations of residue sites and amino acid types, making experimental approaches costly and time-consuming. The Potts model has…
Post-transductional modifications tune the functions of proteins and regulate the collective dynamics of biochemical networks that determine how cells respond to environmental signals. For example, protein phosphorylation and nitrosylation…
The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks…
The interaction between proteins and nucleic acids is crucial for processes that sustain cellular function, including DNA maintenance and the regulation of gene expression and translation. Amino acid mutations in protein-nucleic acid…
Understanding how protein mutations affect protein structure is essential for advancements in computational biology and bioinformatics. We introduce PRIMRose, a novel approach that predicts energy values for each residue given a mutated…
Proteins are responsible for the most diverse set of functions in biology. The ability to extract information from protein sequences and to predict the effects of mutations is extremely valuable in many domains of biology and medicine.…
Control of transcription presides over a vast array of biological processes, including those mediated by gene regulatory circuits that exhibit multistability. Within these circuits, two- and three-gene network motifs are particularly…
A protein's function depends critically on its conformational ensemble, a collection of energy weighted structures whose balance depends on temperature and environment. Though recent deep learning (DL) methods have substantially advanced…
Various biological sensory systems exhibit a response to a relative change of the stimulus, often referred to as fold-change detection. In the last few years fold-change detecting mechanisms, based on transcriptional networks, have been…
The sequence of a protein is not only constrained by its physical and biochemical properties under current selection, but also by features of its past evolutionary history. Understanding the extent and the form that these evolutionary…
In unicellular organisms such as bacteria the same acquired mutations beneficial in one environment can be restrictive in another. However, evolving Escherichia coli populations demonstrate remarkable flexibility in adaptation. The…
In this paper, we consider two stochastic models of gene expression in prokaryotic cells. In the first model, sixteen biochemical reactions involved in transcription, translation and transcriptional regulation in the presence of inducer…
Allosteric regulation is found across all domains of life, yet we still lack simple, predictive theories that directly link the experimentally tunable parameters of a system to its input-output response. To that end, we present a general…
We show how to localize and quantify the functional evolutionary constraints on natural proteins. The method compares the perturbations caused by local sequence variants to the energetics of the protein folding process and to the…
A mutation in a protein-coding gene in DNA can alter the protein structure coded by the same gene. Structurally altered proteins usually lose their functions and sometimes gain an undesirable function instead. These types of mutations and…
From the response to external stimuli to cell division and death, the dynamics of living cells is based on the expression of specific genes at specific times. The decision when to express a gene is implemented by the binding and unbinding…