Dimerization of the transmembrane (TM) adaptor protein DAP12 plays a key role in mediating activation signals through TM-TM association with cell-surface receptors. Herein, we apply the TOXCAT assay and molecular dynamics simulation to analyze dynamics and dimerization of the TM helix of DAP12 in the membrane bilayer. In the TOXCAT assay, we performed site-specific mutagenesis of potential dimerization motifs in the DAP12 TM domain. Instead of the common GxxxG dimerization motif, mutating either of the polar residues Asp-50 and Thr-54 significantly decreased the TOXCAT signal for the dimerization of DAP12 TM domain. Furthermore, through the conformational difference between wild-type and mutant DAP12 TM homodimers, a combined coarse-grained and atomistic molecular dynamics simulation has identified both Asp-50 and Thr-54 at the dimerization interface. The experimental and computational results of the DAP12 TM dimer are in excellent agreement with the previously reported NMR structure obtained in detergent micelles. Such a combination of dynamics simulation and cell-based experiments can be applied to produce insights at the molecular level into the TM-TM association of many other transmembrane proteins.

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Accelerated degradation test (ADT) is generally used to accelerate degradation processes in products to estimate their lifespan and to assess their reliability in a short period of time. How to perform the failure mechanism consistency test is crucial in the application of the ADT method. Existing failure mechanism consistency test methods assume that degradation rates among individual products are the same. However, these methods do not take degradation dispersions caused by manufacturing technologies into consideration. To address this issue, a failure mechanism consistency test method for ADT based on the activation energy invariant method and the likelihood ratio test is proposed. First, a degradation modeling method for ADT is introduced. Then, the logarithmic maximum likelihood function values of the degradation models are estimated based on the two‐step maximum likelihood estimation (MLE) method. Finally, the decision rule is proposed based on the likelihood ratio test. The method mentioned above is, then, used on the real degradation data of carbon‐film resistors and bullet O‐rings, and its effectiveness is verified. Furthermore, based on the failure mechanism change point in RTV5370 siloxane rubbers, the simulated degradation data are degenerated to compare the proposed method with the method not considering individual differences in different ADT programs and degradation dispersions.

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