Molecular Dynamics of Glucocorticoid Receptor

Molecular Dynamics simulations were performed on an AMD 3970 × CPU@ 3.7 GHz with the support of a NVIDIA GeForce GTX 1080 graphics chip using GROMACS v2018 and the CHARMM36 force field built in the Linux Ubuntu 18 environment^{40 (link),41 (link),48 (link)}. Calculations are based on the GRLBD crystal structure with PDB ID 5NFP, solved by Hemmerling et al.^{39 (link)} The L773P mutation was generated with FoldX while dexamethasone topology was generated with the CGenFF server^{38 (link),49 (link),50 (link)}. The Avogadro program was used to assign the dexamethasone hydrogen atom coordinates^{51 (link)}. The Cgenff_charmm2gmx.py script from the Mac Kerell lab was used to format the ligand topology for GROMACS. The unit cell was defined as a dodecahedron and was solvated in TIP3P water. The protein net charge was neutralized by adding the appropriate Na⁺ and Cl⁻ ions. The energy minimization step and NVT, NPT equilibration steps were performed based on the tutorials and mdp. files provided by Dr. Justin Lemkul (http://www.mdtutorials.com/) with minor modifications⁵² . Production MD for data collection was performed for 100 ns (n = 2) and trajectories were analyzed with the GROMACS toolset. Histograms were visualized with Origin 8.6, hydrophobic interactions with BIOVIA discovery studio and Kyte-Doolitle hydrophobicity was colored using UCSF Chimera^{37 (link),53 (link)}.