Protein features as determinants of wild-type glycoside hydrolase thermostability.
Geertz-Hansen, H. M., Kiemer, L., Nielsen, M., Stanchev, K., Blom, N., Brunak, S. and Petersen, T. N.
Novo Nordisk Foundation Center for Biosustainability, Kemitorvet, Building 220, Technical University of Denmark, DK-2800, Lyngby, Denmark.
Department of Bio and Health Informatics, Kemitorvet, Building 208, Technical University of Denmark, DK-2800, Lyngby, Denmark.
Novozymes A/S, Krogshojvej 36, DK-2880, Bagsvaerd, Denmark.
Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, San Martin, B 1650 HMP, Buenos Aires, Argentina.
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Blegdamsvej 3B, University of Copenhagen, DK-2200, Copenhagen N, Denmark.
Thermostable enzymes for conversion of lignocellulosic biomass into biofuels have significant advantages over enzymes with more moderate themostability due to the challenging application conditions. Experimental discovery of thermostable enzymes is highly cost intensive, and the development of in-silico methods guiding the discovery process would be of high value. To develop such an in-silico method and provide the data foundation of it, we determined the melting temperatures of 602 fungal glycoside hydrolases from the families GH5, 6, 7, 10, 11, 43 and AA9 (formerly GH61). We, then used sequence and homology modeled structure information of these enzymes to develop the ThermoP melting temperature prediction method. Futhermore, in the context of thermostability, we determined the relative importance of 160 molecular features, such as amino acid frequencies and spatial interactions, and exemplified their biological significance. The presented prediction method is made publicly available at This article is protected by copyright. All rights reserved.
Proteins 85(11): 2036-2044 (2017)