Molecular interactions between monoclonal oligomer-specific antibody 5E3 and its amyloid beta cognates.

Oligomeric amyloid β (Aβ) is currently considered the most neurotoxic form of the Aβ peptide implicated in Alzheimer's disease (AD). The molecular structures of the oligomers have remained mostly unknown due to their transient nature. As a result, the molecular mechanisms of interactions between conformation-specific antibodies and their Aβ oligomer (AβO) cognates are not well understood.

Initial Structural Models of the Aβ42 Dimer from Replica Exchange Molecular Dynamics Simulations.

Experimental characterization of the molecular structure of small amyloid (A)β oligomers that are currently considered as toxic agents in Alzheimer's disease is a formidably difficult task due to their transient nature and tendency to aggregate. Such structural information is of importance because it can help in developing diagnostics and an effective therapy for the disease. In this study, molecular simulations and protein-protein docking are employed to explore a possible connection between the structure of Aβ monomers and the properties of the intermonomer interface in the Aβ42 dimer.

Long-time scale fluctuations of human prion protein determined by restrained MD simulations.

Cellular prion protein (PrP(C)) has the ability to trigger transmissible lethal diseases after in vivo maturation into a toxic amyloidogenic misfolded form (PrP(Sc)). Here, we use hydrogen exchange protection factors in restrained molecular dynamics simulations to characterize long-time scale fluctuations in human PrP(C). We find that the regions of residues 138-141 and 183-192 form new β-strands in several exchange-competent structures.