To probe the conformational requirements of loop 1 in the Pin1 WW domain, the residues at the i + 2 and i + 3 positions of a beta -turn within this loop were replaced by dPro-Gly and Asn-Gly, which are known to prefer the conformations required at the i + 1 and i + 2 positions of type II ' and type I ' beta -turns. Conformational specificity or lack thereof was further examined by incorporating into the i + 2 and i + 3 positions a non-a-amino acid-based beta -turn mimetic (4-(2 ' -aminoethyl)-6-dibenzofuran propionic acid residue, i), which was designed to replace the i + 1 and i + 2 positions of beta -turns. All these Pin WW variants are monomeric and folded as discerned by analytical ultracentrifugation, NMR, and CD. They exhibit cooperative two-state transitions and display thermodynamic stability within 0.5 kcal/mol of the wild-type WW domain, demonstrating that the acquisition of native structure and stability does not require a specific sequence and, by extension, conformation within loop i. However, it could be that these loop 1 mutations alter the kinetics of antiparallel beta -sheet folding, which will be addressed by subsequent kinetic studies.