Prediction of folding rates and transition-state placement from native-state geometry.
A variety of experimental and theoretical studies have established that the folding process of monomeric proteins is strongly influenced by the topology of the native state. In particular, folding times have been shown to correlate well with the contact order, a measure of contact locality. Our investigation focuses on identifying additional topologic properties that correlate with experimentally measurable quantities, such as folding rates and transition-state placement, for both two- and three-state folders. The validation against data from 40 experiments shows that a particular topological property that measures the interdependence of contacts, termed cliquishness or clustering coefficient, can account with statistically significant accuracy both for the transition state placement and especially for folding rates. The observed correlations can be further improved by optimally combining the distinct topological information captured by cliquishness and contact order.
Micheletti
Cristian
C
International School for Advanced Studies (SISSA) and INFM, Trieste, Italy. michelet@sissa.it
D007700:Kinetics; D015233:Models, Statistical; D015394:Molecular Structure; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results; D040681:Structural Homology, Protein
D011506:Proteins