why do protein folding rates correlate with metrics of native topology为什么蛋白质折叠速率与本地拓扑指标.pdf

Why Do Protein Folding Rates Correlate with Metrics of Native Topology? ´ ´ 1,2 1,3,4 1,2 5 Patrıcia F. N. Faısca *, Rui D. M. Travasso , Andrea Parisi , Antonio Rey ´ ´ ´ ´ 1 Centro de Fısica da Materia Condensada, Universidade de Lisboa, Lisboa, Portugal, 2 Departamento de Fısica, Universidade de Lisboa, Lisboa, Portugal, 3 Centro de Fısica ´ Computacional and Departamento de Fısica, Universidade de Coimbra, Coimbra, Portugal, 4 Center of Ophthalmology and Vision Sciences, Institute for Biomedical ´ ´ ´ Research in Light and Image (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal, 5 Departamento de Quımica Fısica I, Facultad de Ciencias Quımicas, Universidad Complutense, Madrid, Spain Abstract For almost 15 years, the experimental correlation between protein folding rates and the contact order parameter has been under scrutiny. Here, we use a simple simulation model combined with a native-centric interaction potential to investigate the physical roots of this empirical observation. We simulate a large set of circular permutants, thus eliminating dependencies of the folding rate on other protein properties (e.g. stability). We show that the rate-contact order correlation is a consequence of the fact that, in high contact order structures, the contact order of the transition state ensemble closely