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Funnel‐like organization in sequence space determines the distributions of protein stability and folding rate preferred by evolution
Author(s) -
Xia Yu,
Levitt Michael
Publication year - 2004
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.10563
Subject(s) - sequence space , funnel , sequence (biology) , folding (dsp implementation) , protein folding , stability (learning theory) , space (punctuation) , mathematics , population , statistical physics , biological system , physics , computer science , mathematical analysis , biology , chemistry , genetics , banach space , engineering , demography , electrical engineering , organic chemistry , nuclear magnetic resonance , machine learning , sociology , operating system
To understand the physical and evolutionary determinants of protein folding, we map out the complete organization of thermodynamic and kinetic properties for protein sequences that share the same fold. The exhaustive nature of our study necessitates using simplified models of protein folding. We obtain a stability map and a folding rate map in sequence space. Comparison of the two maps reveals a common organizational principle: optimality decreases more or less uniformly with distance from the optimal sequence in the sequence space. This gives a funnel‐shaped optimality surface. Evolutionary dynamics of a sequence population on these two maps reveal how the simple organization of sequence space affects the distributions of stability and folding rate preferred by evolution. Proteins 2004. © 2004 Wiley‐Liss, Inc.