Using structural motif templates to identify proteins with DNA binding function

Nucleic Acids Research
Susan JonesJ M Thornton

Abstract

This work describes a method for predicting DNA binding function from structure using 3-dimensional templates. Proteins that bind DNA using small contiguous helix-turn-helix (HTH) motifs comprise a significant number of all DNA-binding proteins. A structural template library of seven HTH motifs has been created from non-homologous DNA-binding proteins in the Protein Data Bank. The templates were used to scan complete protein structures using an algorithm that calculated the root mean squared deviation (rmsd) for the optimal superposition of each template on each structure, based on C(alpha) backbone coordinates. Distributions of rmsd values for known HTH-containing proteins (true hits) and non-HTH proteins (false hits) were calculated. A threshold value of 1.6 A rmsd was selected that gave a true hit rate of 88.4% and a false positive rate of 0.7%. The false positive rate was further reduced to 0.5% by introducing an accessible surface area threshold value of 990 A2 per HTH motif. The template library and the validated thresholds were used to make predictions for target proteins from a structural genomics project.

References

Sep 5, 1992·Journal of Molecular Biology·L J Beamer, C O Pabo
May 11, 1992·Nucleic Acids Research·A Bairoch
Oct 24, 1991·Nature·S C Harrison
Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Sep 1, 1995·Trends in Biochemical Sciences·R A Sayle, E J Milner-White
Aug 17, 1995·Nature·Y KimT A Steitz
Oct 7, 1993·Nature·Y KimP B Sigler
Apr 1, 1996·Computer Applications in the Biosciences : CABIOS·R Hughey, A Krogh
Aug 15, 1997·Structure·C A OrengoJ M Thornton
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J SchultzC P Ponting
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·C G Nevill-ManningD L Brutlag
May 1, 1999·Journal of Molecular Biology·S JonesJ M Thornton
Jun 11, 1999·The Journal of Biological Chemistry·T A Steitz
Dec 26, 2001·Nucleic Acids Research·Alex BatemanErik L L Sonnhammer
Mar 6, 2002·The Journal of Biological Chemistry·Rong-Guang ZhangAlexei Savchenko
Jul 20, 2002·Journal of Molecular Biology·Nicholas M Luscombe, Janet M Thornton
Dec 19, 2002·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Giri NarasimhanKalai Mathee

❮ Previous
Next ❯

Citations

Jul 17, 2008·Comparative and Functional Genomics·Susan Jones, Janet M Thornton
Feb 11, 2005·Journal of Structural and Functional Genomics·William A McLaughlinHelen M Berman
Mar 24, 2004·Current Opinion in Chemical Biology·Susan Jones, Janet M Thornton
Dec 5, 2003·Nucleic Acids Research·Susan JonesJanet M Thornton
Sep 10, 2004·Nucleic Acids Research·Hugh P ShanahanJanet M Thornton
Apr 16, 2005·Nucleic Acids Research·Marialuisa Pellegrini-Calace, Janet M Thornton
Jun 28, 2005·Nucleic Acids Research·Roman A LaskowskiJanet M Thornton
Nov 15, 2005·Nucleic Acids Research·Nitin BhardwajHui Lu
Jun 3, 2008·Nucleic Acids Research·Mu Gao, Jeffrey Skolnick
Aug 22, 2008·PLoS Computational Biology·Shula Shazman, Yael Mandel-Gutfreund
Jun 23, 2009·Journal of Computer-aided Molecular Design·Deepak BandyopadhyayAlexander Tropsha
Mar 11, 2015·International Journal of Molecular Sciences·Jingna SiRongling Wu
Aug 1, 2008·Computational Biology and Chemistry·R SreekanthS S Rajan
Feb 24, 2007·Journal of Molecular Biology·James D WatsonJanet M Thornton
Mar 28, 2008·Journal of Computational Chemistry·Anna MarabottiAndrea Mozzarelli
Dec 23, 2006·Proteins·Jonathan J EllisSusan Jones
May 15, 2004·Molecular & Cellular Proteomics : MCP·LaToya S JonesC Russell Middaugh
Oct 16, 2016·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Jun HuDong-Jun Yu
Apr 24, 2009·Journal of Biomolecular Structure & Dynamics·K Krishna KumarP N Suganthan
Apr 9, 2019·Briefings in Bioinformatics·Sijia ZhangJunfeng Xia
Dec 29, 2019·BMC Bioinformatics·Binh P NguyenSusanto Rahardja

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.