Quantitative prediction of amyloid fibril growth of short peptides from simulations: calculating association constants to dissect side chain importance.
Quantitative prediction of the fibril growth properties of different peptides is conducted with a molecular dynamics approach. Association constants of small peptides used as a model for amyloid formation are calculated, and the results show very good agreement with experiments. Also the free-energy differences associated with two important interactions that characterize fibril growth, namely cross-beta-sheet and lateral interactions, are obtained. These two interactions show different dependencies on the physicochemical properties of the side chains, explaining the variation in fibril morphologies between different peptides.
Wolf
Maarten G
MG
Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands. m.g.wolf@tudelft.nl
Jongejan
Jaap A
JA
Laman
Jon D
JD
de Leeuw
Simon W
SW
D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D010455:Peptides / Q000737:chemistry*; D011336:Probability
D000682:Amyloid; D010455:Peptides