  In this study we evaluate, at full atomic detail, the folding processes of
two small helical proteins, the B domain of protein A and the Villin headpiece.
Folding kinetics are studied by performing a large number of ab initio Monte
Carlo folding simulations using a single transferable all-atom potential. Using
these trajectories, we examine the relaxation behavior, secondary structure
formation, and transition-state ensembles (TSEs) of the two proteins and
compare our results with experimental data and previous computational studies.
To obtain a detailed structural information on the folding dynamics viewed as
an ensemble process, we perform a clustering analysis procedure based on graph
theory. Moreover, rigorous pfold analysis is used to obtain representative
samples of the TSEs and a good quantitative agreement between experimental and
simulated Fi-values is obtained for protein A. Fi-values for Villin are also
obtained and left as predictions to be tested by future experiments. Our
analysis shows that two-helix hairpin is a common partially stable structural
motif that gets formed prior to entering the TSE in the studied proteins. These
results together with our earlier study of Engrailed Homeodomain and recent
experimental studies provide a comprehensive, atomic-level picture of folding
mechanics of three-helix bundle proteins.
