Journal
BIOLOGICAL REVIEWS
Volume 98, Issue 1, Pages 243-262Publisher
WILEY
DOI: 10.1111/brv.12905
Keywords
protein folds; protein fold switches; protein similarity networks; protein structure networks; protein evolution
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Proteins play a crucial role in connecting genotype and phenotype, but understanding the relationship between protein sequence and structure, and applying this knowledge to predict function, is challenging. Investigating the space of protein folds can provide insights into protein evolution and function.
Proteins form arguably the most significant link between genotype and phenotype. Understanding the relationship between protein sequence and structure, and applying this knowledge to predict function, is difficult. One way to investigate these relationships is by considering the space of protein folds and how one might move from fold to fold through similarity, or potential evolutionary relationships. The many individual characterisations of fold space presented in the literature can tell us a lot about how well the current Protein Data Bank represents protein fold space, how convergence and divergence may affect protein evolution, how proteins affect the whole of which they are part, and how proteins themselves function. A synthesis of these different approaches and viewpoints seems the most likely way to further our knowledge of protein structure evolution and thus, facilitate improved protein structure design and prediction.
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