A Conformational Study of GM1 headgroup with amyloid beta(1-42) protein to identify the molecular specificity and interactions in Alzheimer's disease

作者：Shine Devarajan^*; Sundara Sharmila Jeya

来源：Research Journal of Biotechnology, 2014, 9(12): 33-40.

• Amyloid beta (A beta 1-42)
• GM1 headgroup
• Molecular dynamics
• Amyloid aggregation
• Alzheimer's disease

Amyloid beta protein (A beta) aggregation is the hallmark of Alzheimer's disease. Recent accumulating evidence suggested that a unique complex, monosialo ganglioside (GM1)-bound A beta possesses a high potential to facilitate this protein assembly. This interaction is pre-requisite for the initial recognition and further progression of beta amyloid aggregation in neuron cells. However there are no defined molecular interactions that lead to conformational changes between beta amyloid (A beta 1-42) protein and the GM1 headgroup. Moreover, the sialic acid moiety in headgroup plays a major role in molecular recognition.
In order to study an atomic level conformational basis of this particular complex, we conducted an all atom molecular dynamics simulation of beta amyloid (A beta 1-42) peptide with monosialo ganglioside headgroup in solvent system. Our MD simulation revealed that upon binding of GM1 to the peptide leads to the alteration in the alpha-helix backbone especially at the C-terminal. The complex was stabilized by a network of hydrogen bonds. However, the amino acids His(13), Leu(17) and Phe(20) play a major role in determining the interactions and stability with GM1. Thus, our conformational analysis helps to identify the structural alterations and interacting points on amyloid beta protein by GM1 headgroup.

• 出版日期2014-12