The authors emphasized the importance of hydrophobic collapse in the formation of the hairpin turn, affirmed the existence of a misfolded state and proposed an additional compact intermediate state that precedes folding or misfolding. A different formation pathway was proposed by Enemark et al. that relies on hairpin turn formation rather than hydrophobic collapse in order to stabilize the protein. Despite these arguments, the consensus of these studies recognize the major metastable states (native, misfolded and unfolded), the importance of the Tyr2-Trp9 edge-to-face interaction in defining the native state, and the Asp3O-Gly7N interaction in defining the misfolded state. Kührová et al. used replica-exchange MD in explicit solvent to evaluate four different force fields' ability to reproduce solution NMR measurements for chignolin: 50 AMBER99SB, AMBER ff03*, AMBER ff03w (a version of ff03 optimized for use with TIP4P/2005), and CHARMM22/CMAP (all except AMBER ff03w used TIP3P ). A key finding of this work was that the AMBER force fields predict a misfolded state with significant population, while the CHARMM force field does not. The authors attributed this to differences in glycine parameters between the two kinds of force fields, and the critical role of Gly-7 in the betaturn formation of chignolin. The authors also noted that separate studies show AMBER parameters to more accurately predict solution NMR observables for glycine, and that a representative ensemble of folded and misfolded conformations better reproduced nuclear magnetic resonance (NMR) observables for chignolin.