Insight into the protein solubility driving forces with neural attention

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Abstract

Protein solubility is a key aspect for many biotechnological, biomedical and industrial processes, such as the production of active proteins and antibodies. In addition, understanding the molecular determinants of the solubility of proteins may be crucial to shed light on the molecular mechanisms of diseases caused by aggregation processes such as amyloidosis. Here we present SKADE, a novel Neural Network protein solubility predictor and we show how it can provide novel insight into the protein solubility mechanisms, thanks to its neural attention architecture. First, we show that SKADE positively compares with state of the art tools while using just the protein sequence as input. Then, thanks to the neural attention mechanism, we use SKADE to investigate the patterns learned during training and we analyse its decision process. We use this peculiarity to show that, while the attention profiles do not correlate with obvious sequence aspects such as biophysical properties of the aminoacids, they suggest that N- and C-termini are the most relevant regions for solubility prediction and are predictive for complex emergent properties such as aggregation-prone regions involved in beta-amyloidosis and contact density. Moreover, SKADE is able to identify mutations that increase or decrease the overall solubility of the protein, allowing it to be used to perform large scale in-silico mutagenesis of proteins in order to maximize their solubility.

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APA

Raimondi, D., Orlando, G., Fariselli, P., & Moreau, Y. (2020). Insight into the protein solubility driving forces with neural attention. PLoS Computational Biology, 16(4). https://doi.org/10.1371/journal.pcbi.1007722

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