In silico study on the effect of F 19 T mutation on amyloid - β peptide ( 10 - 35 )

1. Abstract 2. Introduction 3. Methods and materials 3.1. MD simulations 3.2. Calculations of intramolecular contacts 3.3. Identification of a reverse loop 3.4. Identification of the SLS 3.5. Conformational Clustering 4. Results 4.1. The simulations are close to equilibrium and the results are consistent with NMR experiments 4.2. The analysis of overall topologies reveals that the WT favors Loop 22-28 and the F19T mutant favors Loop 15-23 4.3. The analysis of electrostatic interactions reveals the importance of the interactions between the E22 and D23 side chains and peptide backbone 4.4. The F19T mutation breaks the central hydrophobic core (CHC) and weakens the interactions between the CHC and the C-terminal (CT) 4.5. Structures and stabilities of Loop 22-28 4.6. Structures and stabilities of Loop 15-23 4.7. Structures and stabilities of the SLS 5. Discussions and conclusions 5.1. Intrinsic stability of the loop 22-28 in the WT Aβ peptide 5.2. Significant changes in Aβ conformation by F19T mutation 5.3. Possible roles of D23-K28 salt bridge and E22/D23-bakbone hydrogen bonds in the Aβ folding 5.4. Importance of SLS to deposition 6. Acknowledgements 7. References