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Abstract According to the Principle of Minimal Frustration, folded proteins can only have a minimal number of strong energetic conflicts in their native states. However, not all interactions are energetically optimized for folding but some remain in energetic conflict, i.e. they are highly frustrated. This remaining local energetic frustration has been shown to be statistically correlated with distinct functional aspects such as protein-protein interaction sites, allosterism and catalysis. Fuelled by the recent breakthroughs in efficient protein structure prediction that have made available good quality models for most proteins, we have developed a strategy to calculate local energetic frustration within large protein families and quantify its conservation over evolutionary time. Based on this evolutionary information we can identify how stability and functional constraints have appeared at the common ancestor of the family and have been maintained over the course of evolution. Here, we present FrustraEvo, a web server tool to calculate and quantify the conservation of local energetic frustration in protein families.
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Key aspects of the past 30 years of protein design
Abstract Proteins are the workhorse of life. They are the building infrastructure of living systems; they are the most efficient molecular machines known, and their enzymatic activity is still unmatched in versatility by any artificial system. Perhaps proteins’ most remarkable feature is their modularity. The large amount of information required to specify each protein’s function is analogically encoded with an alphabet of just ∼20 letters. The protein folding problem is how to encode all such information in a sequence of 20 letters. In this review, we go through the last 30 years of research to summarize the state of the art and highlight some applications related to fundamental problems of protein evolution.
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- Award ID(s):
- 2019745
- PAR ID:
- 10416883
- Date Published:
- Journal Name:
- Reports on Progress in Physics
- Volume:
- 85
- Issue:
- 8
- ISSN:
- 0034-4885
- Page Range / eLocation ID:
- 086601
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1088/1361-6633/ac78ef
