mGPfusion: Predicting protein stability changes with Gaussian process kernel learning and data fusion

Proteins are used in various applications by pharmaceutical, food, fuel, and many other industries and their usage is growing steadily (Kirk et al., 2002; Sanchez and Demain, 2010). Proteins have important advantages over chemical catalysts, as they are derived from renewable resources, are biodegradable and are often highly selective (Cherry and Fidantsef, 2003). Protein engineering is used to further improve the properties of proteins, for example to enhance their catalytic activity, modify their substrate specificity or to improve their thermostability (Rapley and Walker, 2000). Increasing the stability is an important aspect of protein engineering, as the proteins used in industry should be stable in the industrial process conditions, which often involve higher than ambient temperature and non-aqueous solvents (Bommarius et al., 2011). The properties of a protein are modified by introducing alterations to its amino acid sequence. Mutations in general tend to be destabilising, and if too many destabilising mutations are implemented, the protein may not remain functional without compensatory stabilising mutations (Tokuriki and Tawfik, 2009). The stability of a protein can be defined as the difference in Gibbs energy G between the folded and unfolded (or native and denaturated) state of the protein.