摘要
Using blind dock method,we find that thioflavin-T(ThT) can bind to both monomers and fibrils of the full-length β-amyloid peptide(Aβ1-42) and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand(ThT) and substrate(Aβ1-42) are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.
Using blind dock method,we find that thioflavin-T（ThT） can bind to both monomers and fibrils of the full-length β-amyloid peptide（Aβ1-42） and has a higher binding affinity to the fibrils.It is shown that the hydrophobic interaction between the ligand（ThT） and substrate（Aβ1-42） are stronger than hydrogen bonds.Furthermore,ThT tends to be located near the C-terminus of Aβ monomer through hydrophobic and electrostatic interactions,while it tends to contact the residues Met35 and Gly27 of the fibril surface mainly through hydrophobic interaction.Finally,according to the docking results and ThT fluorescence assay,a kinetic equation is proposed to deduce the aggregation rate coefficient of Aβ1-42.
基金
supported by the National Natural Science Foundation of China(20825206,20091350914 & 90913003)
the Specialized Research Fund for the Doctoral Program of Higher Education (20100002110069)
