Processing of CASP15 targets into evaluation units (EUs) and assigning them to evolutionary-based prediction classes is presented in this study. The targets were first split into structural domains based on compactness and similarity to other proteins. Models were then evaluated against these domains and their combinations. The domains were joined into larger EUs if predictors' performance on the combined units was similar to that on individual domains. Alternatively, if most predictors performed better on the individual domains, then they were retained as EUs. As a result, 112 evaluation units were created from 77 tertiary structure prediction targets. The EUs were assigned to four prediction classes roughly corresponding to target difficulty categories in previous CASPs: TBM (template-based modeling, easy or hard), FM (free modeling), and the TBM/FM overlap category. More than a third of CASP15 EUs were attributed to the historically most challenging FM class, where homology or structural analogy to proteins of known fold cannot be detected.

Interactions of amyloid-β (Aβ) peptides with neuronal membrane are associated with the development of Alzheimer's disease (AD). Ganglioside monosialotetrahexosylganglioside (GM1) lipids have been shown to form clusters that induce the structural conversion of Aβ and promote the incorporation of Aβ into the membrane via the membrane surface electrical potential. Prior to the onset of AD symptoms, GM1 clusters may not have formed but the concentration of GM1 may have already changed, and our question is whether this early concentration modification affects the structure and mechanical properties of the membrane. Using one model for healthy cell membranes and three models for AD cell membranes, we carry out 2 µs all-atom molecular dynamics simulations for each model to compare the structure and elasticity of the two membrane types. The simulations show that at the physiological concentration, 1%-3%, GM1 does not form clusters. The reduction of the GM1 lipid does not significantly alter the area per lipid, the membrane thickness, and the lipid order parameters of the AD membranes. However, the dipole potential, the bending, and twist moduli are decreased for the AD membranes. We suggest that these changes in the AD membranes are factors that could trigger the interaction and incorporation of Aβ to the membranes. Finally, we show that changes in the sphingomyelin lipid concentrations do not affect the membrane structure and elasticity.