Artigo sobre a proteína ci2

doi:10.1006/jmbi.2000.3693 available online at http://www.idealibrary.com on

J. Mol. Biol. (2000) 298, 937±953

Topological and Energetic Factors: What Determines the Structural Details of the Transition State Ensemble and ``En-route'' Intermediates for Protein Folding? An Investigation for Small Globular Proteins
Cecilia Clementi*, Hugh Nymeyer and Jose Nelson Onuchic Â
Department of Physics University of California at San Diego, La Jolla, CA 920930319, USA Recent experimental results suggest that the native fold, or topology, plays a primary role in determining the structure of the transition state ensemble, at least for small, fast-folding proteins. To investigate the extent of the topological control of the folding process, we studied the folding of simpli®ed models of ®ve small globular proteins constructed using a Go-like potential to retain the information about the native structures but drastically reduce the energetic frustration and energetic heterogeneity among residue-residue native interactions. By comparing the structure of the transition state ensemble (experimentally determined by È-values) and of the intermediates with those obtained using our models, we show that these energetically unfrustrated models can reproduce the global experimentally known features of the transition state ensembles and ``en-route'' intermediates, at least for the analyzed proteins. This result clearly indicates that, as long as the protein sequence is suf®ciently minimally frustrated, topology plays a central role in determining the folding mechanism.
# 2000 Academic Press

*Corresponding author

Keywords: protein folding; transition state; folding intermediate; È-value analysis; molecular dynamics simulations

Introduction
Our understanding of the protein folding problem has been thoroughly changed by the new view that has emerged in the last decade. This new view, based on the energy landscape theory and funnel concept (Leopold et al., 1992; Bryngelson et