Emergence of Protein Fold Families through Rational Design
Author Information
Author(s): Ding Feng, Dokholyan Nikolay V
Primary Institution: University of North Carolina at Chapel Hill
Hypothesis
Subtle structural changes due to accumulating mutations in homologous families lead to distinct packing of the protein core and novel compositions of core residues.
Conclusion
The study demonstrates that analogous proteins emerge when a backbone structure deviates only 1–2 Å from the original structure.
Supporting Evidence
- Proteins with sequence similarity higher than 25%–30% usually adopt a similar structure and are called homologs.
- Analogous proteins emerge when the backbone structures deviate only 1–2 Å from the original structure.
- The conservation of amino acids in designed sequences recapitulates that of naturally occurring sequences.
Takeaway
Scientists created a computer program to design proteins, showing that small changes in protein structure can lead to new types of proteins.
Methodology
Developed a molecular modeling and design toolkit, Medusa, to computationally design protein sequences corresponding to the same fold family.
Limitations
The study's model may not fully capture the complexities of natural protein evolution.
Statistical Information
P-Value
1.0 × 10−9
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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