------------------- GENERAL INFORMATION 1. Title: Simulation data from the publication - Le Huray et al., Sci. Adv. 8, eabp9688 (2022), "Characterization of the membrane interactions of phospholipase C\u03b3 reveals key features of the active enzyme" 2. Description: A repository of simulation data from the publication "Characterization of the membrane interactions of phospholipase C\u03b3 reveals key features of the active enzyme". PLC\u03b3 enzymes are autoinhibited in resting cells and form key components of intracellular signaling that are also linked to disease development. Insights into physiological and aberrant activation of PLCg require understanding of an active, membrane bound form, that can hydrolyse inositol-lipid substrates. Here we demonstrate that PLC\u03b31 cannot bind membranes unless the autoinhibition is disrupted. Through extensive MD simulations and experimental evidence, we characterise membrane binding by the catalytic core domains and reveal novel sites of lipid interaction. The identified sites act in synergy, overlap with autoinhibitory interfaces and are shown to be critical for the phospholipase activity in cells. This work provides direct evidence that PLC\u03b31 is inhibited through obstruction of its membrane-binding surfaces by the regulatory region and that activation must shift PLC\u03b31 to a conformation competent for membrane binding. Knowledge of the critical sites of membrane interaction extends the mechanistic framework for activation, dysregulation, and therapeutic intervention. This dataset contains: - DATASET1: coarse-grained MD simulation data for the binding of the WT PLC\u03b31 core domains to a model membrane - DATASET 2: coarse-grained MD simulation data for the binding of a mutant (clone E) variant of the PLC\u03b31 core domains to a model membrane - DATASET 3: coarse-grained MD simulation data for the binding of the SH3 domain of PLC\u03b31 to a model membrane - DATASET 4: coarse-grained MD simulation data for the binding of the tandem nSH2-cSH3 domains of PLC\u03b31 to a model membrane - DATASET 5: coarse-grained MD simulation data for the binding of the sPH domain of PLC\u03b31 to a model membrane - DATASET 6: atomistic MD simulation data of the membrane bound state of the wild-type (WT) core domains 3. Author information A. Principal Investigator Contact Information Name: Dr Antreas Kalli Institution: University of Leeds Email: a.kalli@leeds.ac.uk B. Dataset Creator Contact Information Name: Kyle Le Huray Institution: University of Leeds Email: bskipl@leeds.ac.uk ------------------- DATA & FILE OVERVIEW For convenience, the data has been divided into 6 dataset zip files: [dataset] [description] 1 Coarse-grained MD simulation data for the binding of the WT PLC\u03b31 core domains to a model membrane 2 Coarse-grained MD simulation data for the binding of a mutant (clone E) variant of the PLC\u03b31 core domains to a model membrane 3 Coarse-grained MD simulation data for the binding of the SH3 domain of PLC\u03b31 to a model membrane 4 Coarse-grained MD simulation data for the binding of the tandem nSH2-cSH3 domains of PLC\u03b31 to a model membrane 5 Coarse-grained MD simulation data for the binding of the sPH domain of PLC\u03b31 to a model membrane 6 Atomistic MD simulation data of the membrane bound state of the wild-type (WT) core domains FILE NAME CONVENTIONS Files prefixed with "md." correspond to production simulations. Files prefixed with "eq." correspond to equilibration of the simulation system prior to production simulations. Files prefixed with "em." correspond to energy minimization of the simulation system prior to equilibration. .pdb files are Protein Data Bank format protein coordinate files .tpr files are GROMACS binary input run files for a simulation .gro files are the coordinates from the final frame of a simulation .xtc files are the GROMACS simulation trajectories, thinned to 10% of their original size (due to memory limitations) by only writing every 10th frame from the original. ------------------- METHODOLOGICAL INFORMATION 1. Description of methods used for collection/generation of data: These data were generated using coarse grained molecular dynamics simulations of the obtained protein structure, and a model of the inner leaflet of the mammalian plasma membrane. These were run using v2.1 of the Martini CG force field and GROMACS 5.0.7 (CG simulations) or CHARMM36 force field and GROMACS 2016 (atomistic simulations). 2. Methods for processing the data: Due to storage limitations the trajectories have been thinned to 10% of their original frames. 3. This work was undertaken on ARC3 and ARC4, part of the High Performance Computing facilities at the University of Leeds, UK.