Journal article
Evaluating the predictions of the protein stability change upon single amino acid substitutions for the FXN CAGI5 challenge
Human mutation, Vol.40(9), pp.1392-1399
09/2019
PMID: 31209948
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Abstract
Frataxin (FXN) is a highly conserved protein found in prokaryotes and eukaryotes that is required for efficient regulation of cellular iron homeostasis. Experimental evidence associates amino acid substitutions of the FXN to Friedreich Ataxia, a neurodegenerative disorder. Recently, new thermodynamic experiments have been performed to study the impact of somatic variations identified in cancer tissues on protein stability. The Critical Assessment of Genome Interpretation (CAGI) data provider at the University of Rome measured the unfolding free energy of a set of variants (FXN challenge data set) with far‐UV circular dichroism and intrinsic fluorescence spectra. These values have been used to calculate the change in unfolding free energy between the variant and wild‐type proteins at zero concentration of denaturant (ΔΔGH2O). The FXN challenge data set, composed of eight amino acid substitutions, was used to evaluate the performance of the current computational methods for predicting the ΔΔGH2O value associated with the variants and to classify them as destabilizing and not destabilizing. For the fifth edition of CAGI, six independent research groups from Asia, Australia, Europe, and North America submitted 12 sets of predictions from different approaches. In this paper, we report the results of our assessment and discuss the limitations of the tested algorithms.
Details
- Title
- Evaluating the predictions of the protein stability change upon single amino acid substitutions for the FXN CAGI5 challenge
- Creators
- Castrense Savojardo - University of BolognaMaria Petrosino - Sapienza University of RomeGiulia Babbi - University of BolognaSamuele Bovo - University of BolognaCarles Corbi-Verge - University of TorontoRita Casadio - University of BolognaPiero Fariselli - University of Torino (Italy, Torino)Lukas Folkman - Griffith University (Australia, Gold Coast)Aditi Garg - Indian Institute of ScienceMostafa Karimi - Texas A&M UniversityPanagiotis Katsonis - Baylor College of MedicinePhilip M. Kim - University of TorontoOlivier Lichtarge - Baylor College of MedicinePier Luigi Martelli - University of BolognaAlessandra Pasquo - Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali di FrascatiDebnath Pal - Indian Institute of ScienceYang Shen - Texas A&M UniversityAlexey V. Strokach - University of TorontoPaola Turina - University of BolognaYaoqi Zhou - Griffith University (Australia, Gold Coast)Gaia Andreoletti - University of California, BerkeleySteven E. Brenner - University of California, BerkeleyRoberta Chiaraluce - Sapienza University of RomeValerio Consalvi - Sapienza University of RomeEmidio Capriotti - University of Bologna
- Publication Details
- Human mutation, Vol.40(9), pp.1392-1399
- Publisher
- Wiley
- Number of pages
- 8
- Identifiers
- 991013341144902368
- Copyright
- © 2019 Wiley Periodicals, Inc.
- Academic Unit
- Faculty of Science and Engineering
- Language
- English
- Resource Type
- Journal article