TY - JOUR
T1 - Coevolutionary information, protein folding landscapes, and the thermodynamics of natural selection
AU - Morcos, Faruck
AU - Schafer, Nicholas P.
AU - Cheng, Ryan R.
AU - Onuchic, José N.
AU - Wolynes, Peter G.
PY - 2014/8/26
Y1 - 2014/8/26
N2 - The energy landscape used by nature over evolutionary timescales to select protein sequences is essentially the same as the one that folds these sequences into functioning proteins, sometimes in microseconds. Weshow that genomic data, physical coarse-grained free energy functions, and family-specific information theoretic models can be combined to give consistent estimates of energy landscape characteristics of natural proteins. One such characteristic is the effective temperature Tsel at which these foldable sequences have been selected in sequence space by evolution. Tsel quantifies the importance of folded-state energetics and structural specificity for molecular evolution. Across all protein families studied, our estimates for T sel are well below the experimental folding temperatures, indicating that the energy landscapes of natural foldable proteins are strongly funneled toward the native state.
AB - The energy landscape used by nature over evolutionary timescales to select protein sequences is essentially the same as the one that folds these sequences into functioning proteins, sometimes in microseconds. Weshow that genomic data, physical coarse-grained free energy functions, and family-specific information theoretic models can be combined to give consistent estimates of energy landscape characteristics of natural proteins. One such characteristic is the effective temperature Tsel at which these foldable sequences have been selected in sequence space by evolution. Tsel quantifies the importance of folded-state energetics and structural specificity for molecular evolution. Across all protein families studied, our estimates for T sel are well below the experimental folding temperatures, indicating that the energy landscapes of natural foldable proteins are strongly funneled toward the native state.
KW - Elastic effects
KW - Energy landscape theory
KW - Funneled landscapes
KW - Information theory
KW - Selection temperature
UR - http://www.scopus.com/inward/record.url?scp=84906706579&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906706579&partnerID=8YFLogxK
U2 - 10.1073/pnas.1413575111
DO - 10.1073/pnas.1413575111
M3 - Article
C2 - 25114242
AN - SCOPUS:84906706579
SN - 0027-8424
VL - 111
SP - 12408
EP - 12413
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 34
ER -