ArticleGenome biology2001
Quod erat demonstrandum? The mystery of experimental validation of apparently erroneous computational analyses of protein sequences.
Article in Genome biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 73 citations in OpenAlex.
- Article
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- Conservation of the separase regulatory domain.Biology direct · 2018Article
- CDvist: a webserver for identification and visualization of conserved domains in protein sequences.Bioinformatics (Oxford, England) · 2015Article
- Conserved Functional Motifs and Homology Modeling to Predict Hidden Moonlighting Functional Sites.Frontiers in bioengineering and biotechnology · 2015Review
- Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins.Journal of virology · 2014Article
- Grand challenges in bioinformatics and computational biology.Frontiers in genetics · 2011Article
- The human Ago2 MC region does not contain an eIF4E-like mRNA cap binding motif.Biology direct · 2009Article
- Bacteria as computers making computers.FEMS microbiology reviews · 2009Review
- It is computation time for bacteriology!Journal of bacteriology · 2009Article
- Dark matter in a deep-sea vent and in human mouth.Environmental microbiology · 2007Article
- Effective function annotation through catalytic residue conservation.Proceedings of the National Academy of Sciences of the United States of America · 2005Article
- EFICAz: a comprehensive approach for accurate genome-scale enzyme function inference.Nucleic acids research · 2004Article
- Cysteinyl-tRNA(Cys) formation in Methanocaldococcus jannaschii: the mechanism is still unknown.Journal of bacteriology · 2004Article
- The Arabidopsis basic/helix-loop-helix transcription factor family.The Plant cell · 2003Article
- Comparative genomics of Archaea: how much have we learned in six years, and what's next?Genome biology · 2003Review
- The methionine salvage pathway in Bacillus subtilis.BMC microbiology · 2002Article
- The complete genome of hyperthermophile Methanopyrus kandleri AV19 and monophyly of archaeal methanogens.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundComputational predictions are critical for directing the experimental study of protein functions. Therefore it is paradoxical when an apparently erroneous computational prediction seems to be supported by experiment.
resultsWe analyzed six cases where application of novel or conventional computational methods for protein sequence and structure analysis led to non-trivial predictions that were subsequently supported by direct experiments. We show that, on all six occasions, the original prediction was unjustified, and in at least three cases, an alternative, well-supported computational prediction, incompatible with the original one, could be derived. The most unusual cases involved the identification of an archaeal cysteinyl-tRNA synthetase, a dihydropteroate synthase and a thymidylate synthase, for which experimental verifications of apparently erroneous computational predictions were reported. Using sequence-profile analysis, multiple alignment and secondary-structure prediction, we have identified the unique archaeal 'cysteinyl-tRNA synthetase' as a homolog of extracellular polygalactosaminidases, and the 'dihydropteroate synthase' as a member of the beta-lactamase-like superfamily of metal-dependent hydrolases.
conclusionsIn each of the analyzed cases, the original computational predictions could be refuted and, in some instances, alternative strongly supported predictions were obtained. The nature of the experimental evidence that appears to support these predictions remains an open question. Some of these experiments might signify discovery of extremely unusual forms of the respective enzymes, whereas the results of others could be due to artifacts.
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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.