2004/01/28 by Jesse D Bloom, Jesse D. Bloom, Claus O. Wilke +4
Biochemistry, Genetics and Molecular Biology · #Evolvability #Function (biology) #Gene Regulatory Network Analysis #Protein Structure and Dynamics #Protein evolution #Protein function #Protein stability #RNA and protein synthesis mechanisms #Selection (genetic algorithm) #Simple (philosophy) #Stability (learning theory) #q-bio.BM
paper · pdf · doi:10.1016/s0006-3495(04)74329-5
published as Biophysical Journal, 86:2758-2764 (2004) · Biophysical Journal in press
arxiv created 2004/01/28 · openalex publication_date 2004/05/01 · arxiv updated 2009/12/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
Functional proteins must fold with some minimal stability to a structure that can perform a biochemical task. Here we use a simple model to investigate the relationship between the stability requirement and the capacity of a protein to evolve the function of binding to a ligand. Although our model contains no built-in tradeoff between stability and function, proteins evolved function more efficiently when the stability requirement was relaxed. Proteins with both high stability and high function evolved more efficiently when the stability requirement was gradually increased than when there was constant selection for high stability. These results show that in our model, the evolution of function is enhanced by allowing proteins to explore sequences corresponding to marginally stable structures, and that it is easier to improve stability while maintaining high function than to improve function while maintaining high stability. Our model also demonstrates that even in the absence of a fundamental biophysical tradeoff between stability and function, the speed with which function can evolve is limited by the stability requirement imposed on the protein.