TY - JOUR
T1 - The Flory isolated-pair hypothesis is not valid for polypeptide chains
T2 - Implications for protein folding
AU - Pappu, Rohit V.
AU - Srinivasan, Rajgopal
AU - Rose, George D.
PY - 2000/11/7
Y1 - 2000/11/7
N2 - Using an all-atom representation, we exhaustively enumerate all sterically allowed conformations for short polyalanyl chains. Only intrachain interactions are considered, including one adjustable parameter, a favorable backbone energy (e.g., a peptide hydrogen bond). The counting is used to reevaluate Flory's isolated-pair hypothesis, the simplifying assumption that each φ,ψ pair is sterically independent. This hypothesis is a conceptual linchpin in helix-coil theories and protein folding. Contrary to the hypothesis, we find that systematic local steric effects can extend beyond nearest-chain neighbors and can restrict the size of accessible conformational space significantly. As a result, the entropy price that must be paid to adopt any specific conformation is far less than previously thought.
AB - Using an all-atom representation, we exhaustively enumerate all sterically allowed conformations for short polyalanyl chains. Only intrachain interactions are considered, including one adjustable parameter, a favorable backbone energy (e.g., a peptide hydrogen bond). The counting is used to reevaluate Flory's isolated-pair hypothesis, the simplifying assumption that each φ,ψ pair is sterically independent. This hypothesis is a conceptual linchpin in helix-coil theories and protein folding. Contrary to the hypothesis, we find that systematic local steric effects can extend beyond nearest-chain neighbors and can restrict the size of accessible conformational space significantly. As a result, the entropy price that must be paid to adopt any specific conformation is far less than previously thought.
KW - Helix-coil theory
KW - Levinthal paradox
UR - http://www.scopus.com/inward/record.url?scp=0033730431&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033730431&partnerID=8YFLogxK
U2 - 10.1073/pnas.97.23.12565
DO - 10.1073/pnas.97.23.12565
M3 - Article
C2 - 11070081
AN - SCOPUS:0033730431
SN - 0027-8424
VL - 97
SP - 12565
EP - 12570
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 - 23
ER -