Many biological processes are mediated by complex interactions between DNA and proteins. Transcription factors, various polymerases, nucleases and histones recognize and bind DNA with different levels of binding specificity. To understand the physical mechanisms that allow proteins to recognize DNA and achieve their biological functions, it is important to analyze structures of DNA-protein complexes in detail. DNAproDB is a web-based interactive tool designed to help researchers study these complexes. DNAproDB provides an automated structure-processing pipeline that extracts structural features from DNA-protein complexes. The extracted features are organized in structured data files, which are easily parsed with any programming language or viewed in a browser. We processed a large number of DNA-protein complexes retrieved from the Protein Data Bank and created the DNAproDB database to store this data. Users can search the database by combining features of the DNA, protein or DNA-protein interactions at the interface. Additionally, users can upload their own structures for processing privately and securely. DNAproDB provides several interactive and customizable tools for creating visualizations of the DNA-protein interface at different levels of abstraction that can be exported as high quality figures. All functionality is documented and freely accessible at http://dnaprodb.usc.edu.
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http://dx.doi.org/10.1093/nar/gkx272 | DOI Listing |
Gene expression is coordinated by a multitude of transcription factors (TFs), whose binding to the genome is directed through multiple interconnected epigenetic signals, including chromatin accessibility and histone modifications. These complex networks have been shown to be disrupted during aging, disease, and cancer. However, profiling these networks across diverse cell types and states has been limited due to the technical constraints of existing methods for mapping DNA:Protein interactions in single cells.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Pritzker School of Molecular Engineering, University of Chicago, Chicago, Illinois 60637, United States.
Coarse-grained models have become ubiquitous in biomolecular modeling tasks aimed at studying slow dynamical processes such as protein folding and DNA hybridization. These models can considerably accelerate sampling but it remains challenging to accurately and efficiently restore all-atom detail to the coarse-grained trajectory, which can be vital for detailed understanding of molecular mechanisms and calculation of observables contingent on all-atom coordinates. In this work, we introduce FlowBack as a deep generative model employing a flow-matching objective to map samples from a coarse-grained prior distribution to an all-atom data distribution.
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Cancer metabolism is sustained both by enhanced aerobic glycolysis, characteristic of the Warburg phenotype, and oxidative metabolism. Cell survival and proliferation depends on a dynamic equilibrium between mitochondrial function and glycolysis, which is heterogeneous between tumors and even within the same tumor. During oxidative phosphorylation, electrons from NADH and FADH originated in the tricarboxylic acid cycle flow through complexes of the electron transport chain.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Department of Microbiology and Plant Pathology, University of California, Riverside, CA, USA.
Transcriptional regulation allows cells to execute developmental programs, maintain homeostasis, and respond to intra- and extracellular signals. Central to these processes are promoters, which in eukaryotes are sequences upstream of genes that bind transcription factors (TFs) and which recruit RNA polymerase to initiate mRNA synthesis. Valuable tools for studying promoters include reporter genes, which can be used to indicate when and where genes are activated.
View Article and Find Full Text PDFMethods Mol Biol
December 2024
Genome Integrity and Cancers, UMR 9019 CNRS, Université-Paris-Saclay, Gustave Roussy, Villejuif, France.
Homologous recombination (HR) is a high-fidelity DNA repair pathway that uses a homologous DNA sequence as a template. Recombinase proteins are the central HR players in the three kingdoms of life. RecA/RadA/Rad51 assemble on ssDNA, generated after the processing of double-strand breaks or stalled replication forks into an active and dynamic presynaptic helical nucleofilament.
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