The 'topology' of a protein native structure refers to the pattern of noncovalent contacts among its amino acid residues. Diverse folding rates of natural small single-domain proteins are known to correlate well with simple parameters derived from these patterns. Here we extend our investigation of possible physical underpinning of this remarkable topology-rate relationship by applying continuum Gō-like C α Langevin modelling to 13 small proteins. Folding rates simulated at transition

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... are well correlated with D , a 'topomer search model' (TSM) parameter which equals the number of nonlocal contacts in a protein's native structure. This modelling success in mimicking experimental topology-rate relationships is largely a conformational entropic effect: while transition states are results of large entropy-energy compensations, the trend of variation of the activation free energy G ‡ versus D in the model is dominated by G ‡ 's entropic component. Interestingly, the activation conformational entropy S ‡ is well correlated (negatively) with the Boltzmann-averaged number of nonlocal contacts ‡ D in the putative transition state ensemble. Thus, for the present Gō-like explicit-chain models, D 's ability to predict rates is rooted in its correlation with ‡ D . However, the model transition states are much more diffuse than that postulated by TSM because ‡ D is significantly smaller than D .