1. ABOUT THE DATASET -------------------- Title: Simulation data from the publication "Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilisation to the plasma membrane" Creator(s): Chrysa Soteriou Organisation(s): University of Leeds Rights-holder(s):Unless otherwise stated, Copyright 2024 University of Leeds Publication Year: 2024 Description: A repository of simulation data from the publication "Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilisation to the plasma membrane". Here we provide new molecular insight into the first step of AKT activation where AKT binds to the plasma membrane and its orientation is stabilised in a bilayer with lateral heterogeneity (Lo-Ld phase coexistence). We have applied coarse-grained and atomistic molecular simulations and molecular and cell biology approaches and demonstrate that AKT recruitment to the membrane occurs via a secondary binding site in the AKT Pleckstrin Homology domain that acts cooperatively with the known canonical binding site. We showed that disrupting either the canonical or secondary binding sites the membrane localisation and AKT activity is attenuated. Given the precision with which we have identified the protein-lipid interactions, the study offers new directions for AKT-targeted therapy and for testing small molecules to target these specific amino acid-PIP molecular bonds. This dataset contains: - DATASET 1: coarse-grained MD simulation data for the binding of the WT AKT-PH to a model membrane - DATASET 2: coarse-grained MD simulation data for the binding of the mut1 AKT-PH to a model membrane - DATASET 3: coarse-grained MD simulation data for the binding of the mut2 AKT-PH to a model membrane- DATASET 4: coarse-grained MD simulation data for the binding of the mut3 AKT-PH to a model membrane- DATASET 5: coarse-grained MD simulation data for the binding of the WT AKT-PH to a model membrane without PIP lipids- DATASET 6: atomistic MD simulation data for the binding of the WT AKT-PH to a model membrane. Cite as: Soteriou C. et al. (2024) Simulation data from the publication "Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilisation to the plasma membrane". University of Leeds. [Dataset] https://doi.org/10.5518/1313. Related publication: Soteriou et al., Two cooperative lipid binding sites within the pleckstrin homology domain are necessary for AKT binding and stabilisation to the plasma membrane, Structure, 2024, (Accepted) 2. TERMS OF USE --------------- Unless otherwise stated, this dataset is licensed under a Creative Commons Attribution 4.0 International Licence: https://creativecommons.org/licenses/by/4.0/. 3. Author Information ---------------------------------- A. Principal Investigators Contact Information Name: Dr James Thorne Institution: University of Leeds Email: j.l.thorne@leeds.ac.uk Name: Dr Antreas Kalli Institution: University of Leeds Email: a.kalli@leeds.ac.uk B. Dataset Creator Contact Information Name: Chrysa Soteriou Institution: University of Leeds Email: fscs@leeds.ac.uk 4. CONTENTS ----------- 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 AKT-PH to a model membrane 2 coarse-grained MD simulation data for the binding of the mut1 AKT-PH to a model membrane 3 coarse-grained MD simulation data for the binding of the mut2 AKT-PH to a model membrane 4 coarse-grained MD simulation data for the binding of the mut3 AKT-PH to a model membrane 5 coarse-grained MD simulation data for the binding of the WT AKT-PH to a model membrane without PIP lipids 6 atomistic MD simulation data for the binding of the WT AKT-PH to a model membrane .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, trajectories skipping every 100 frames (due to memory limitations) 5. METHODS ---------- - Description of methods used for collection/generation of data: These data were generated using coarse grained and atomistic molecular dynamics simulations of the obtained protein structure and a phase separated model 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). - Methods for processing the data: Due to storage limitations the trajectories the -skip 100 option was used to thin the trajectories by skipping every 100 frames. - This work was undertaken on ARC3 and ARC4, part of the High Performance Computing facilities at the University of Leeds, UK.