Publications

Authors:

Turina, Paola; Dal Cortivo, Giuditta; Enriquez Sandoval, Carlos A; Alexov, Emil; Ascher, David B; Babbi, Giulia; Bakolitsa, Constantina; Casadio, Rita; Fariselli, Piero; Folkman, Lukas; Kamandula, Akash; Katsonis, Panagiotis; Li, Dong; Lichtarge, Olivier; Martelli, Pier Luigi; Panday, Shailesh Kumar; Pires, Douglas E V; Portelli, Stephanie; Pucci, Fabrizio; Rodrigues, Carlos H M; Rooman, Marianne; Savojardo, Castrense; Schwersensky, Martin; Shen, Yang; Strokach, Alexey V; Sun, Yuanfei; Woo, Junwoo; Radivojac, Predrag; Brenner, Steven E; Dell'Orco, Daniele; Capriotti, Emidio

Title:

Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

A Stampa

Referee:

Sì

Name of journal:

Human Genetics

ISSN of journal:

0340-6717

N° Volume:

First published online: 23 December 2024

Page numbers:

1-13

Keyword:

Calmodulin (CaM); melting temperature (Tm); thermodynamic stability; Sixth Critical Assessment of Genome Interpretation (CAGI6); amino acid substitutions; prediction accuracy

Short description of contents:

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.

Note:

Paola Turina and Giuditta Dal Cortivo have co-first authorship

Web page:

https://doi.org/10.1007/s00439-024-02720-y

Product ID:

143615

Handle IRIS:

11562/1148729

Last Modified:

January 5, 2025

Bibliographic citation:

Turina, Paola; Dal Cortivo, Giuditta; Enriquez Sandoval, Carlos A; Alexov, Emil; Ascher, David B; Babbi, Giulia; Bakolitsa, Constantina; Casadio, Rita; Fariselli, Piero; Folkman, Lukas; Kamandula, Akash; Katsonis, Panagiotis; Li, Dong; Lichtarge, Olivier; Martelli, Pier Luigi; Panday, Shailesh Kumar; Pires, Douglas E V; Portelli, Stephanie; Pucci, Fabrizio; Rodrigues, Carlos H M; Rooman, Marianne; Savojardo, Castrense; Schwersensky, Martin; Shen, Yang; Strokach, Alexey V; Sun, Yuanfei; Woo, Junwoo; Radivojac, Predrag; Brenner, Steven E; Dell'Orco, Daniele; Capriotti, Emidio, Assessing the predicted impact of single amino acid substitutions in calmodulin for CAGI6 challenges «Human Genetics» , vol. First published online: 23 December 2024 , 2024 , pp. 1-13

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