Xu, Q;
Tang, Q;
Katsonis, P;
Lichtarge, O;
Jones, D;
Bovo, S;
Babbi, G;
... Dunbrack, RL; + view all
(2017)
Benchmarking predictions of allostery in liver pyruvate kinase in CAGI4.
Human Mutation
, 38
(9)
pp. 1123-1131.
10.1002/humu.23222.
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Abstract
The Critical Assessment of Genome Interpretation (CAGI) is a global community experiment to objectively assess computational methods for predicting phenotypic impacts of genomic variation. One of the 2015–2016 competitions focused on predicting the influence of mutations on the allosteric regulation of human liver pyruvate kinase. More than 30 different researchers accessed the challenge data. However, only four groups accepted the challenge. Features used for predictions ranged from evolutionary constraints, mutant site locations relative to active and effector binding sites, and computational docking outputs. Despite the range of expertise and strategies used by predictors, the best predictions were marginally greater than random for modified allostery resulting from mutations. In contrast, several groups successfully predicted which mutations severely reduced enzymatic activity. Nonetheless, poor predictions of allostery stands in stark contrast to the impression left by more than 700 PubMed entries identified using the identifiers “computational + allosteric.” This contrast highlights a specialized need for new computational tools and utilization of benchmarks that focus on allosteric regulation.
| Type: | Article |
|---|---|
| Title: | Benchmarking predictions of allostery in liver pyruvate kinase in CAGI4 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/humu.23222 |
| Publisher version: | http://dx.doi.org/10.1002/humu.23222 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | allosteric effect; CAGI experiment; liver pyruvate kinase; missense mutation |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1547713 |
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