Structural Insights into the two sequential folding transition states of the PB1 domain of NBR1 from φ value analysis and biased molecular dynamics simulations

作者：Chen Ping; Evans Clare Louise; Hirst Jonathan D; Searle Mark S^*

来源：Biochemistry, 2011, 50(1): 125-135.

DOI：10.1021/bi1016793

• Different distributions
• Dynamic structure
• Folded state
• Folding pathway
• Folding transition state
• High energy
• Molecular dynamics simulations
• Polypeptide chain
• Secondary structures
• Solvent accessibility
• Structural heterogeneity
• Structural insights
• Transition state
• Value analysis

The PB1 domain of NBR1 folds via a single pathway mechanism involving two sequential energy barriers separated by a high-energy intermediate. The structural ensemble representing each of the two transition states (TS1 and TS2) has been calculated using experimental φ values and biased molecular dynamics simulations. Both TS1 and TS2 represent compact states (βTS1 = 0.71, and βTS2 = 0.93) but are defined by quite different distributions of φ values, degrees of structural heterogeneity, and nativelike secondary structure. TS1 forms a heterogeneous ensemble of dynamic structures, representing a global collapse of the polypeptide chain around a set of weak nativelike contacts. In contrast, TS2 has a high proportion of nativelike secondary structure, which is reflected in an extensive distribution of high φ values. Two snapshots along the folding pathway of the PB1 domain reveal insights into the malleability, the solvent accessibility, and the timing of nativelike core packing that stabilizes the folded state.

• 出版日期2011