Fig. 4.
Energy landscape of Aβ aggregation changes with zinc concentration. Energy landscapes near 330 K were obtained from all conformation in all 64 replicas at 330 and 333 K. The PMFs at 365 K are from conformations at 363 and 366 K. (A) The PMFs of 4Zn2+-8Aβ42 near 330 K point to highly ordered β-sheet oligomers separated from the less ordered conformers by a low barrier, indicating that aggregation can readily take place. (B) At the higher temperature (365 K), the energy landscape favors this ordered state with a higher β-sheet population for the 4Zn2+-8Aβ42 system. (C) The 8Zn2+-8Aβ42 system represents the higher zinc concentration with 1∶1 Zn2+∶Aβ42 ratio. At 330 K, the energy landscape indicates that the highly ordered β-sheet oligomers are less populated. (D) At the higher temperature (365 K), the highly ordered β-sheet oligomers are more populated for the 8Zn2+-8Aβ42 system.