Published February 18, 2022 | Version v1
Dataset Open

Simulations for: Patched 1 regulates Smoothened by controlling sterol binding to its extracellular cysteine-rich domain.

  • 1. Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, California, United States of America
  • 2. Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
  • 3. Department of Biochemistry, University of Oxford, Oxford, UK
  • 4. Department of Developmental Biology and Taylor Family Institute for Innovative Psychiatric Research, Washington University School of Medicine, St. Louis, Missouri, United States of America

Description

Atomistic simulations of Smoothened:

Atomistic molecular dynamics simulations of glycosylated mouse Smoothened (mSMO) and human Smoothened (hSMO) in distinct liganded states:

- mSMO in an apo state (mSMO_apo)

- mSMO with TMD cholesterol bound (mSMO_chol_TMD)

- mSMO with CRD cholesterol bound (mSMO_chol_CRD)

- mSMO with cholesterol bound to the CRD and TMD (mSMO_2chol_TMD_CRD)

- mSMO bound to CRD cholesterol and Smoothened agonist (SAG) (mSMO_chol_CRD_SAG)

- mSMO bound to CRD and TMD cholesterols, SAG and an intracellular nanobody (mSMO_2chol_SAG_nanobody)

- mSMO bound to CRD and TMD cholesterol and with an additional cholesterol bound at a proposed 'mid' position (mSMO_3chol)

- hSMO bound to CRD cholesterol and SAG (hSMO_chol_CRD_SAG)

 

All simulations were run for 5x 300 ns. The active mSMO conformation was obtained from the Protein Data Bank (PDB ID: 6O3C). The hSMO structure was determined using X-ray crystallography as outlined within this study.  

File description for each system:

- md_fit_firstframe.pdb : Initial frame used for atomistic simulations (replicate 1, each replicate equilibrated independently). 

- md_fit_X.xtc : Gromacs trajectory file for each replicate (X=replicate number). 

Files

SMO_simulations.zip

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