Secondary structure provides a template for the folding of nearby polypeptides

作者：Kameda Tomoshi; Takada Shoji^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(47): 17765-17770.

DOI：10.1073/pnas.0602632103

• energy landscape
• generalized Born
• polyproline II
• protein folding
• replica exchange

Although protein structures are primarily encoded by their sequences, they are also critically dependent on environmental factors such as solvents and interactions with other molecules. Here we investigate how the folding-energy landscape of a short peptide is altered by interactions with another peptide, by per forming atomistic replica-exchange molecular dynamics simulations of polyalanines in various environments. We analyzed the free-energy landscapes of Ala(7) and Ala(8) in isolation, near an a-helix template, and near a beta-strand template. The isolated Ala(7) and Ala(8) at 270 K were mainly in polyproline II helix conformations and in equilibrium between the a-helix and polyproline II helix, respectively, in harmony with the experiment. Interestingly, we found remarkably strong secondary-structure "templating"; namely, the alpha-helix template enhanced a-helix conformation and the P-strand template induced beta-strand conformation in the simulated MO. The alpha-helix template lowered the nearby dielectric constant, which strengthened hydrogen bonds in the simulated Ala(8), leading to alpha-helix stabilization. The beta-strand template provided hydrogen bond positions to the simulated Ala(8), sharply inducing beta-strand structure. With or without templates, the energy landscape of Ala8 is always funnel-like and centered at the alpha-helix conformation, whereas entropic contribution disfavors the alpha-helix, leading to subtle competition. Secondary-structure templating may play a critical role in protein conformation dynamics in the cellular environment.

• 出版日期2006-11-21