Effects of turn stability and side-chain hydrophobicity on the folding of β-structures.
Key elements of β-structure folding include hydrophobic core collapse, turn formation, and assembly of backbone hydrogen bonds. In the present folding simulations of several β-hairpins and β-sheets (peptide 1, protein G B1 domain peptide, TRPZIP2, TRPZIP4, 20mer, and 20mer(D)P6D), the folding free-energy landscape as a function of several reaction coordinates corresponding to the three key elements indicates apparent dependence on turn stability and side-chain hydrophobicity, which demonstrates different folding mechanisms of similar β-structures of varied sequences. Turn stability is found to be the key factor in determining the formation order of the three structural elements in the folding of β-structures. Moreover, turn stability and side-chain hydrophobicity both affect the stability of backbone hydrogen bonds. The three-stranded β-sheets fold through a three-state transition in which the formation of one hairpin always takes precedence over the other. The different stabilities of two anti-parallel hairpins in each three-stranded β-sheet are shown to correlate well with the different levels of their hydrophobic interactions.
Shao
Qiang
Q
College of Chemical and Molecular Engineering, Peking University, Beijing, China.
Wei
Haiyan
H
Gao
Yi Qin
YQ
D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins; C539234:Trpzip2 protein