Editorial: Machine learning, epistasis, and protein engineering: From sequence-structure-function relationships to regulation of metabolic pathways

Abstract

Editorial on the Research Topic Machine learning, epistasis, and protein engineering: From sequencestructure-function relationships to regulation of metabolic pathways Epistasis is a term originating from genomics and describes the non-additivity of effects of gene interactions on functional parameters (Phillips, 2008). Both within and between genes, epistasis plays a fundamental role in the ability of protein sequences to evolve (Breen et al., 2012).In protein sciences, epistasis reflects non-linearity effects, ie., non-additive impacts, resulting from interactions between mutations within a protein sequence (Reetz, 2013). The evolution of proteins cannot be understood without the knowledge of the epistasis phenomena (non-additive mutational effects) that take place within them. Indeed, epistasis can reverse the effect of a mutation from beneficial to deleterious. Likewise, thanks to epistasis phenomena, the conservation of a neutral mutation during evolution can lead to beneficial effects of greater amplitude. Interactions between mutated amino acids, as well as intramolecular interaction networks that can be set up following mutations, condition the function (Acevedo-Rocha et al., 2021). While it is clear that understanding sequence-structure-function relationships, and in particular

Empowering Protein Engineering through Recombination of Beneficial Substitutions

“…Furthermore, positive epistasis is crucial in protein engineering because it gives insight into sequence-structure-function interactions and can lead to the creation of new proteins with superior features. [25] Xinyue Wang received her Bachelor of Engineering degree from Ludong University in 2021. Currently, she is pursuing her master's degree at Nanjing Normal University under the dedicated guidance of Associate Prof. Dr. Xiujuan Li.…”

“…In this situation, the substitutions cancel each other out, resulting in a milder phenotype. Furthermore, positive epistasis is crucial in protein engineering because it gives insight into sequence‐structure‐function interactions and can lead to the creation of new proteins with superior features [25] …”