Journal article
Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges
Human genetics, Vol.144(2-3), pp.113-125
03/2025
PMID: 39714488
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Abstract
Recent thermodynamic and functional studies have been conducted to evaluate the impact of amino acid substitutions on Calmodulin (CaM). The Critical Assessment of Genome Interpretation (CAGI) data provider at University of Verona (Italy) measured the melting temperature (Tm) and the percentage of unfolding (%unfold) of a set of CaM variants (CaM challenge dataset). Thermodynamic measurements for the equilibrium unfolding of CaM were obtained by monitoring far-UV Circular Dichroism as a function of temperature. These measurements were used to determine the Tm and the percentage of protein remaining unfolded at the highest temperature. The CaM challenge dataset, comprising a total of 15 single amino acid substitutions, was used to evaluate the effectiveness of computational methods in predicting the Tm and unfolding percentages associated with the variants, and categorizing them as destabilizing or not. For the sixth edition of CAGI, nine independent research groups from four continents (Asia, Australia, Europe, and North America) submitted over 52 sets of predictions, derived from various approaches. In this manuscript, we summarize the results of our assessment to highlight the potential limitations of current algorithms and provide insights into the future development of more accurate prediction tools. By evaluating the thermodynamic stability of CaM variants, this study aims to enhance our understanding of the relationship between amino acid substitutions and protein stability, ultimately contributing to more accurate predictions of the effects of genetic variants.
Details
- Title
- Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges
- Creators
- Paola Turina - University of BolognaGiuditta Dal Cortivo - University of VeronaCarlos A Enriquez Sandoval - University of BolognaEmil Alexov - Clemson UniversityDavid B Ascher - Baker Heart and Diabetes InstituteGiulia Babbi - University of BolognaConstantina Bakolitsa - University of California, BerkeleyRita Casadio - University of BolognaPiero Fariselli - University of TurinLukas Folkman - Griffith University (Australia, Gold Coast)Akash Kamandula - Northeastern UniversityPanagiotis Katsonis - Baylor College of MedicineDong Li - Université Libre de BruxellesOlivier Lichtarge - Baylor College of MedicinePier Luigi Martelli - University of BolognaShailesh Kumar Panday - Clemson UniversityDouglas E V Pires - The University of MelbourneStephanie Portelli - Baker Heart and Diabetes InstituteFabrizio Pucci - Université Libre de BruxellesMarianne Rooman - Université Libre de BruxellesCarlos H M Rodrigues - Baker Heart and Diabetes InstituteCastrense Savojardo - University of BolognaMartin Schwersensky - Université Libre de BruxellesYang Shen - Texas A&M UniversityAlexey V Strokach - University of TorontoYuanfei Sun - Texas A&M UniversityJunwoo Woo - 3 Billion (South Korea)Predrag Radivojac - Northeastern UniversitySteven E Brenner - University of California, BerkeleyDaniele Dell'Orco - University of VeronaEmidio Capriotti - University of Bologna
- Publication Details
- Human genetics, Vol.144(2-3), pp.113-125
- Publisher
- Springer Nature
- Identifiers
- 991013341143702368
- Copyright
- © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.
- Academic Unit
- Faculty of Science and Engineering
- Language
- English
- Resource Type
- Journal article