HER2 W452C Structural Models and Molecular Dynamics Data

This repository contains structural models, representative HADDOCK3 docking structures, molecular dynamics trajectories, and topology files associated with the study: "Experimental and structural analysis of HER2 W452C supports a model of disulfide-network perturbation and altered receptor organization." The deposited files support the structural analyses of the HER2 W452C extracellular variant and the comparison of three predefined cysteine/disulfide states. Structural states Three HER2 structural states were examined: Repository name Structural state WT Wild-type HER2 with the native C475-C504 disulfide W452C HER2 W452C mutant with the native C475-C504 disulfide retained W452Cds HER2 W452C conditional disulfide-swapped model containing C452-C475 in place of the native C475-C504 disulfide The W452Cds state is a conditional perturbation model used to examine the structural consequences of disrupting the native C475-C504 disulfide. It should not be interpreted as evidence that the C452-C475 disulfide forms in cells. Near-full-length HER2 structural models The following PDB files contain the near-full-length HER2 models used for structural analysis and molecular dynamics system preparation: WT.pdbWild-type HER2 with native C475-C504. W452C.pdbW452C mutant with native C475-C504 retained and C452 unpaired. W452Cds.pdbConditional W452C model containing C452-C475 with C504 unpaired. These models contain the HER2 ectodomain, transmembrane region, and intracellular kinase region assembled into a common near-full-length structural framework. HADDOCK3 structures The following files contain representative receptor-pair structures generated during the HADDOCK3 analyses: C452-C452.pdbRepresentative C452-C452 docking configuration shown in Figure 3d. C452-C504.pdbRepresentative C452-C504 configuration shown in Figure 4c. C504-C504.pdbRepresentative C504-C504 configuration shown in Figure 4d. These structures illustrate candidate receptor geometries examined in the study. They should not be interpreted as experimentally identified cellular disulfide linkages. Molecular dynamics trajectories Three independent 100-ns molecular dynamics trajectories are provided for each structural state. The files are compressed in MD_results.zip: Wild type WT_100ns.dcd WT_2_100ns.dcd WT_3_100ns.dcd WT_step5_input.psf W452C with native C475-C504 W452C_100ns.dcd W452C_2_100ns.dcd W452C_3_100ns.dcd W452C_step5_input.psf Conditional W452C C452-C475 state W452Cds_100ns.dcd W452Cds_2_100ns.dcd W452Cds_3_100ns.dcd W452Cds_step5_input.psf Files without _2_ or _3_ correspond to replicate 1. The PSF files provide the corresponding molecular topology required for interpretation of the DCD trajectories. Software and simulation details Detailed model construction, molecular dynamics simulation, structural analysis, cysteine-accessibility analysis, and HADDOCK3 protocols are described in the Methods section of the associated manuscript. The simulations were performed using membrane-embedded HER2 systems with three independently initiated 100-ns trajectories for each structural state. Contact Questions regarding the deposited structural data may be directed to the corresponding authors of the associated manuscript.