Exploration of the mechanism for LPFFD inhibiting the formation of beta-sheet conformation of A beta(1-42) in water.

The main component of senile plaques found in AD brain is amyloid beta-peptide (A beta), and the neurotoxicity and aggregation of A beta are associated with the formation of beta-sheet structure. Experimentally, beta sheet breaker (BSB) peptide fragment Leu-Pro-Phe-Phe-Asp (LPFFD) can combine with A beta, which can inhibit the aggregation of A beta. In order to explore why LPFFD can inhibit the formation of beta-sheet conformation of A beta at atomic level, first, molecular docking is performed to obtain the binding sites of LPFFD on the A beta(1-42) (LPFFD/A beta(1-42)), which is taken as the initial conformation for MD simulations. Then, MD simulations on LPFFD/A beta(1-42) in water are carried out. The results demonstrate that LPFFD can inhibit the conformational transition from alpha-helix to beta-sheet structure for the C-terminus of A beta(1-42), which may be attributed to the hydrophobicity decreasing of C-terminus residues of A beta(1-42) and formation probability decreasing of the salt bridge Asp23-Lys28 in the presence of LPFFD.