Critical assessment of protein intrinsic disorder prediction

NECCI, MARCO; PIOVESAN, DAMIANO; HOQUE, MD TAMJIDUL; WALSH, IAN; IQBAL, SUMAIYA; VENDRUSCOLO, MICHELE; SORMANNI, PIETRO; WANG, CHEN; RAIMONDI, DANIELE; SHARMA, RONESH; ZHOU, YAOQI; LITFIN, THOMAS; GALZITSKAYA, OXANA VALERIANOVNA; LOBANOV, MICHAIL YU.; VRANKEN, WIM; WALLNER, BJÖRN; MIRABELLO, CLAUDIO; MALHIS, NAWAR; DOSZTÁNYI, ZSUZSANNA; ERD?S, GÁBOR; MÉSZÁROS, BÁLINT; GAO, JIANZHAO; WANG, KUI; HU, GANG; WU, ZHONGHUA; SHARMA, ALOK; HANSON, JACK; PALIWAL, KULDIP; CALLEBAUT, ISABELLE; BITARD-FEILDEL, TRISTAN; ORLANDO, GABRIELE; PENG, ZHENLING; XU, JINBO; WANG, SHENG; JONES, DAVID T.; COZZETTO, DOMENICO; MENG, FANCHI; YAN, JING; GSPONER, JÖRG; CHENG, JIANLIN; WU, TIANQI; KURGAN, LUKASZ; PROMPONAS, VASILIS J.; TAMANA, STELLA; MARINO-BUSLJE, CRISTINA; MARTÍNEZ-PÉREZ, ELIZABETH; CHASAPI, ANASTASIA; OUZOUNIS, CHRISTOS; DUNKER, A. KEITH; KAJAVA, ANDREY V.; LECLERCQ, JEREMY Y.; AYKAC-FAS, BURCU; LAMBRUGHI, MATTEO; MAIANI, EMILIANO; PAPALEO, ELENA; CHEMES, LUCIA BEATRIZ; ÁLVAREZ, LUCÍA; GONZÁLEZ-FOUTEL, NICOLÁS S.; IGLE

NATURE METHODS

NATURE PUBLISHING GROUP

Año: 2021 vol. 18 p. 472 - 481

1548-7091

Intrinsically disordered proteins, defying the traditional protein structure?function paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude.