Active site cavities identification of amyloid beta precursor protein: Alzheimer disease study

Abstract

Alzheimer and Parkinson diseases are the major cases of neuro degenerative diseases. The Alzheimer disease pathogenesis is highly complex. Although, various pathologies characterize this disease, amyloid plaques are the hallmark neuropathological lesions in Alzheimer's disease brain. Active site prediction of Amyloid beta (A4) precursor protein (APP) is done to identify the locations of ligand binding sites as well as to predictfunctional similarities between cavities. This information can be used further to estimate the bound ligands' locations. Mis-folding of APP protein can lead to its aggregation, involving a process in which monomers interact to form dimers, oligomers, and eventually insoluble fibrillar deposits. Alzheimer disease is associated with senile plaques and neurofibrillary tangles (NFTs). The Amyloid-beta (Abeta) is a major component of senile plaques that has various pathological effects on cell and organelle function. In the proposed approach, an active site of the APP is obtained by using active site prediction server. The cavity1 is identified as the cavity highest volume with the following amino acid sequence as the active site MQVEKLSRHAPDNFI. This active site has cavity points 70.757 A°, −31.576 A°, −17.547 A° with the cavity volume of 1335 A3.