ArticleProceedings of the National Academy of Sciences of the United States of America2011
Frustration in protein-DNA binding influences conformational switching and target search kinetics.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 127 citations in OpenAlex.
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- Protein target search diffusion-association/dissociation free energy landscape around DNA binding site with flanking sequences.Biophysical journal · 2025Article
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- Single molecule technique unveils the role of electrostatic interactions in ssDNA-gp32 molecular complex stability.RSC advances · 2024Article
- Nonspecific vs. specific DNA binding free energetics of a transcription factor domain protein.Biophysical journal · 2023Article
- An engineered hypercompact CRISPR-Cas12f system with boosted gene-editing activity.Nature chemical biology · 2023Article
- Structural insights into the DNA recognition mechanism by the bacterial transcription factor PdxR.Nucleic acids research · 2023Article
- Conformational Change of Transcription Factors from Search to Specific Binding: AThe journal of physical chemistry. B · 2022Article
- Following the tracks: How transcription factor binding dynamics control transcription.Biophysical journal · 2022Review
- Charge Engineering Improves the Performance of Bst DNA Polymerase Fusions.ACS synthetic biology · 2022Article
- Investigating the Conformational Dynamics of a Y-Family DNA Polymerase during Its Folding and Binding to DNA and a Nucleotide.JACS Au · 2022Article
- Coarse-grained molecular dynamics simulations of base-pair mismatch recognition protein MutS sliding along DNA.Biophysics and physicobiology · 2022Article
- Novel anti-repression mechanism of H-NS proteins by a phage protein.Nucleic acids research · 2021Article
- Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy.PLoS computational biology · 2021Article
- What Are the Molecular Requirements for Protein Sliding along DNA?The journal of physical chemistry. B · 2021Article
- Discrete-state stochastic kinetic models for target DNA search by proteins: Theory and experimental applications.Biophysical chemistry · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapid recognition of DNA target sites involves facilitated diffusion through which alternative sites are searched on genomic DNA. A key mechanism facilitating the localization of the target by a DNA-binding protein (DBP) is one-dimensional diffusion (sliding) in which electrostatic forces attract the protein to the DNA. As the protein reaches its target DNA site, it switches from purely electrostatic binding to a specific set of interactions with the DNA bases that also involves hydrogen bonding and van der Waals forces. High overlap between the DBP patches used for nonspecific and specific interactions with DNA may enable an immediate transition between the two binding modes following target site localization. By contrast, an imperfect overlap may result in greater frustration between the two potentially competing binding modes and consequently slower switching between them. A structural analysis of 125 DBPs indicates frustration between the two binding modes that results in a large difference between the orientations of the protein to the DNA when it slides compared to when it specifically interacts with DNA. Coarse-grained molecular dynamics simulations of in silico designed peptides comprising the full range of frustrations between the two interfaces show slower transition from nonspecific to specific DNA binding as the overlap between the patches involved in the two binding modes decreases. The complex search kinetics may regulate the search by eliminating trapping of the protein in semispecific sites while sliding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.