Impact of Au144 metal clusters on the structural and inhibitory mechanism of Aß42 peptide: A theoretical approach.

One of the main causes for Alzheimer disease is the abnormal self-assembly of the amyloid-beta (Aß) peptide, which in turn forms a toxic ß-rich aggregation. A recent study suggests that gold nanoparticles (AuNPs) can inhibit the Aß aggregation. Nevertheless, the effects of AuNPs on Aß peptide system are still ambiguous and needs exploration that is more detailed. Molecular dynamics simulations have been carried out to investigate the aggregation mechanism of Aß42 peptide for 500 ns. During simulation, C-terminus regions of Met 35-Ala42 residues exhibits ß-sheet conformations. Meanwhile, the Au144MC coordination induces substantial α-helical character, both α-helix and 310-helix structure at 0-500ns, in the region of Asp1-Arg5 and Val36-Ile41 residues. The Au144MC strongly coordinates with Asp1, Ala2, Glu3, Phe4, Asp7, Tyr10 and Gln15 residues that plays the significant effects to loss the ß-sheet geometry in the N-terminal region and it converted into random α-helix, turn and bend conformation. On comparing the RMSF of the Aß42 peptide and Aß42-Au144MC complex shows that the coordination of Au144MC results in greater rigidity of the Aß42 peptide backbone regions with exemptions for the Asp1, Ala2, Glu3, Leu34, Ile41 and Ala42 residues due to the strong binding between the metal cluster and the CHC (Leu17-Ala21) region. The structural stability of the Aß42 peptide and Aß42-Au144MC complex is enhanced by the several intermolecular and intramolecular interactions and it was visibly revealed in the H-bond. From the above results, it is very evident that the Au144MC can be used as inhibitor agent for the oligomerization of Aß42.

In silico studies of the inhibition mechanism of dengue with papain.

Dengue virus is becoming a major global disease; the envelope protein is the major target for vaccine development against Dengue. Nowadays, the attention has focused on developing inhibitors based on Papain is a promising target for treating Dengue. In the present work, the theoretical studies of E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and His159) complexes are analysed by Density Functional Theory (M06-2X/cc-pVDZ) method. Among the E-protein(Cys74-Glu79;Lys110)…Papain(Cys25, Asn175 and Hys159) complexes, E-protein(Glu76)…Papain(Cys25) complex has the highest interaction value of -352.22 kcal/mol. Moreover, the natural bond orbital analysis also supports the above results. The 100 ns Molecular Dynamics simulation reveals that, E-protein(Ala54-Ile129)…Papain(Cys25) complex had the lowest root mean square deviation value of 1 Å compared to the E-protein(Ala54-Ile129)… Papain(Asn175 & His159) complexes. The salt bridge formation between the Asp103 and Lys110 residues are the important stabilizing factor in E-protein(Ala54-Ile129)…Papain(Cys25) complex. This result can extend our knowledge of the functional behaviour of Papain and provides structural insight to target Envelope protein as forthcoming drug targets in Dengue.

The hazardous effects of the environmental toxic gases on amyloid beta-peptide aggregation: A theoretical perspective.

Alzheimer's disease (AD) is one of the leading causes of dementia in elderly people. It has been well documented that the exposure to environmental toxins such as CO, CO2, SO2 and NO2 that are present in the air is considered as a hallmark for the progression of Alzheimer's disease. However, their actual mechanism by which environmental toxin triggers the aggregation of Aß42 peptide at the molecular and atomic levels remain unknown. In this study, molecular dynamics simulation was carried out to study the aggregation mechanism of the Aß42 peptide due to its interaction of toxic gas (CO, CO2, SO2 and NO2). During the 400 ns simulation, all the Aß42 interacted toxic gas (CO, CO2, SO2, and NO2) complexes have smaller Root Mean Square Deviation values when compared to the Aß42 peptide, which shows that the interaction of toxic gases (CO, CO2, SO2, and NO2) would increase the Aß42 peptide structural stability. The radius of gyration analysis also supports that Aß42 interacted CO2 and SO2 complexes have the minimum value in the range of 0.95 nm and 1.5 nm. It is accounted that the Aß42 interacted CO2 and SO2 complexes have a greater compact structure in comparison to Aß42 interacted CO and NO2 complexes. Furthermore, all the Aß42 interacted toxic gas (CO, CO2, SO2, and NO2) complexes exhibited an enhanced secondary structural probability for coil and turn regions with a reduced α-helix probability, which indicates that the interaction of toxic gases may enhance the toxicity and aggregation of Aß42.