DOI: 10.5061/dryad.c59zw3rjm
title: MD simulations data for: Role of the αC-β4 loop in protein kinase structure and dynamics

description: Although the aC-b4 loop is a stable feature of all protein kinases, the
 importance of this motif as a conserved element of secondary structure, as
 well as its links to the hydrophobic architecture of the kinase core, has
 been underappreciated. We first review the motif and then describe how it
 is linked to the hydrophobic spine architecture of the kinase core, which
 we first discovered using a computational tool, Local Spatial Pattern
 (LSP) alignment. Based on NMR predictions that a mutation in this motif
 abolishes the synergistic high-affinity binding of ATP and a pseudo
 substrate inhibitor, we used LSP to interrogate the F100A mutant. This
 comparison highlights the importance of the aC-b4 loop and key residues at
 the interface between the N- and C-lobes. In addition, we delved more
 deeply into the structure of the apo C-subunit, which lacks ATP. While apo
 C-subunit showed no significant changes in backbone dynamics of the aC-b4
 loop, we found significant differences in the side chain dynamics of K105.
 The LSP analysis suggests disruption of communication between the N- and
 C-lobes in the F100A mutant, which would be consistent with the structural
 changes predicted by the NMR spectroscopy.
description: # MD simulations data for: Role of the αC-β4 loop in protein kinase
 structure and dynamics We use AMBER to perform all-atom Molecular Dynamics
 (MD) Simulations ## Description of the zip folder 1. Once the folder is
 unzipped, it creates a data-availability folder 2. Inside this, there are
 multiple folders for different systems. Each folder contains its own
 solvated parameter file (complex_solv.prmtop) and topology
 files/coordinates files (complex_solv.inpcrd) for running an MD
 simulation: ### System folders: ``` Apo (without ligand like ATP or PKI);
 wt-binary (WT PKA protein with ATP/Mg2+); wt-ternary (WT PKA protein with
 ATP/Mg2+/PKI); F100A-binary (mutant system (F100A) with ATP/Mg2+),
 F100A-ternary (mutant system (F100A) with ATP/Mg2+/PKI) ``` Also, it
 contains an input-parameter folder, which contains all the input files for
 running the MD simulations, including: i). Multiple minimization steps:
 (initially restraining the atoms without hydrogen, then protein and ligand
 restraint, followed by only protein restraint and lastly with no
 restraint): step2.0_min.mdin, step2.1_min.mdin, step2.2_min.mdin,
 step2.3_min.mdin and step2.4_min.mdin ii). multiple and slowly heating
 from 0K to 300K: heat1.in, heat2.in, heat3.in, heat4.in, heat5.in,
 heat6.in iii). equilibration: equil.in iv). production simulation of 20
 ns: prod.in 3. Once the input files are ready, then we use running-script
 to run the MD simulation using AMBER in GPU, which contains all the
 descriptions of steps used for running the MD simulation strating from
 minimization, heating, equilibration to production by taking solvated
 parameter files (complex_solv.prmtop) and coordinates files
 (complex_solv.inpcrd) from each system. 4. After MD is performed, we will
 enter into the analysis from the folder analysis; it contains two files:
 distance.in: how to measure different distances between each atom of
 particular residues pca.in: to perform principal component analysis