Neutrality and evolvability of designed protein sequences.
The effect of foldability on protein's evolvability is analyzed by a two-prong approach consisting of a self-consistent mean-field theory and Monte Carlo simulations. Theory and simulation models representing protein sequences with binary patterning of amino acid residues compatible with a particular foldability criteria are used. This generalized foldability criterion is derived using the high temperature cumulant expansion approximating the free energy of folding. The effect of cumulative point mutations on these designed proteins is studied under neutral condition. The robustness, protein's ability to tolerate random point mutations is determined with a selective pressure of stability (ΔΔG) for the theory designed sequences, which are found to be more robust than that of Monte Carlo and mean-field-biased Monte Carlo generated sequences. The results show that this foldability criterion selects viable protein sequences more effectively compared to the Monte Carlo method, which has a marked effect on how the selective pressure shapes the evolutionary sequence space. These observations may impact de novo sequence design and its applications in protein engineering.
Bhattacherjee
Arnab
A
Department of Chemistry, University of Delhi, Delhi 110007, India.
Biswas
Parbati
P
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019143:Evolution, Molecular; D008956:Models, Chemical; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D020539:Sequence Analysis, Protein / Q000379:methods*
D011506:Proteins