Sequence variability of proteins evolutionarily constrained by solution-thermodynamic function.
Focusing on silk fibroin and hemoglobin molecules as templates, we model protein homolog dispersal across sequence-fitness landscapes determined by solution thermodynamics. Landscapes are constructed by inspecting an idealized theoretical phase topology associated with sequence length and hydrophobic-polar composition, comprising liquid-liquid phase separation, gelation and liquid crystalline self-assembly. We then calculate the distribution of homologs in sequence space as steady states of a simple mutation-selection dynamics. The results are consistent with Swiss-Prot bioinformatic data.
Braun
F N
FN
Stockholm Bioinformatics Center, Department of Biochemistry and Biophysics, Stockholm University, 10691 Stockholm, Sweden.
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019281:Dimerization; D019143:Evolution, Molecular; D005349:Fibroins / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D006454:Hemoglobins / Q000737:chemistry / Q000235:genetics; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics; D008956:Models, Chemical; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D047011:Silk; D012996:Solutions; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D006454:Hemoglobins; D019476:Insect Proteins; D011506:Proteins; D047011:Silk; D012996:Solutions; D005349:Fibroins