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

被引：0

作者：

Turina, Paola ^{[1
]}

Dal Cortivo, Giuditta ^{[2
]}

Sandoval, Carlos A. Enriquez ^{[1
]}

Alexov, Emil ^{[3
]}

Ascher, David B. ^{[4
,5
]}

Babbi, Giulia ^{[1
]}

Bakolitsa, Constantina ^{[6
,7
]}

Casadio, Rita ^{[1
]}

Fariselli, Piero ^{[8
]}

Folkman, Lukas ^{[9
]}

Kamandula, Akash ^{[10
]}

Katsonis, Panagiotis ^{[11
]}

Li, Dong ^{[12
]}

Lichtarge, Olivier ^{[11
]}

Martelli, Pier Luigi ^{[1
]}

Panday, Shailesh Kumar ^{[3
]}

Pires, Douglas E. V. ^{[13
]}

Portelli, Stephanie ^{[4
,5
]}

Pucci, Fabrizio ^{[12
]}

Rodrigues, Carlos H. M. ^{[4
]}

Rooman, Marianne ^{[12
]}

Savojardo, Castrense ^{[1
]}

Schwersensky, Martin ^{[12
]}

Shen, Yang ^{[14
]}

Strokach, Alexey V. ^{[15
]}

Sun, Yuanfei ^{[14
]}

Woo, Junwoo ^{[16
]}

Radivojac, Predrag ^{[10
]}

Brenner, Steven E. ^{[6
,7
,17
,18
]}

Dell'Orco, Daniele ^{[2
]}

Capriotti, Emidio ^{[1
,19
]}

机构：

[1] Univ Bologna, Dept Pharm & Biotechnol, I-40126 Bologna, Italy

[2] Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol Chem, I-37134 Verona, Italy

[3] Clemson Univ, Dept Phys & Astron, Clemson, SC 29634 USA

[4] Baker Heart & Diabet Inst, Computat Biol & Clin Informat, Melbourne, Vic 3004, Australia

[5] Univ Queensland, Australian Ctr Ecogenom, Sch Chem & Mol Biosci, St Lucia, Qld 4072, Australia

[6] Univ Calif Berkeley, Dept Plant & Microbial Biol, Berkeley, CA 94720 USA

[7] Univ Calif Berkeley, Ctr Computat Biol, Berkeley, CA USA

[8] Univ Torino, Dept Med Sci, Turin, Italy

[9] Griffith Univ, Inst Integrated & Intelligent Syst, Southport, Qld, Australia

[10] Northeastern Univ, Khoury Coll Comp Sci, Boston, MA 02115 USA

[11] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA

[12] Univ Libre Bruxelles, Computat Biol & Bioinformat, 50 Roosevelt Ave, B-1050 Brussels, Belgium

[13] Univ Melbourne, Sch Comp & Informat Syst, Melbourne, Vic 3053, Australia

[14] Texas A&M Univ, Dept Elect & Comp Engn, College Stn, TX USA

[15] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada

[16] 3 Billion, Seoul 04763, South Korea

[17] Univ Calif Berkeley, Grad Grp Biophys, Berkeley, CA 94720 USA

[18] Univ Calif Berkeley, Ctr Computat Biol, Berkeley, CA 94720 USA

[19] IRCCS Univ Hosp Bologna, Computat Genom Platform, I-40138 Bologna, Italy

来源：

HUMAN GENETICS | 2024年

关键词：

TARGET RECOGNITION; WEB SERVER; STABILITY; MUTATIONS; PROTEINS; DIVERSITY; VARIANTS; SEQUENCE; BINDING;

D O I：

10.1007/s00439-024-02720-y

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：113 / 125

页数：13

共 55 条

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