EVB Parameters For The Manuscript: The Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase

Starting structures, input + parameter files and exemplar analysis scripts for the empirical valence bond (EVB) simulations performed to generate the data for the article: The Essential Functional Interplay of the Catalytic Groups in Acid Phosphatase (in submission). Documentation (Same as in the README.txt file): In this folder, you will find all the items you need to re-run our EVB simulations. You should first be familiar with the EVB method, a good starting point for this can be found here: https://onlinelibrary.wiley.com/doi/book/10.1002/9781119245544 Each subfolder contains the files needed to run the EVB equil and production simulations for a given system. Further, example helper scripts are provided to show the steps used. ### 1. Equilibration part. For each system the input run files for the equilibration are attached alongside the topology and coordinate files. Note that for each replica you need to choose a new random seed (defined in: "dyn_min_wat_noshake.inp") The order of operations for the equil files is as follows: "dyn_min_wat_noshake", "dyn_min_wat", "dyn_min_wat_eq", "dyn_cool", "dyn_min", "dyn_warm30k", "dyn_warm150k", "dyn_warm300k", "dyn_eq300k_{1..20}". Also included is a helper script "1_Example_Create_Equil_Runs.sh" to generate the directories and job scripts (for Slurm architecture) for the 30 replicas per system. ### 2. Production part. The production runs were performed inside each equilibration run folder inside a folder called "EVB_Prod". The file "2_Example_Setup_Prod_Runs.sh" provides an example of how to setup for production simulations after the equilibration run has complete. Take care to add the final restart file to the production folders working directory (see the script attached) ### 3. Mapping part. The mapping protocol used for the enzyme reactions to determine both the reaction and activation free energies are described in the Supplementary Methods. The file "3_Example_Map_Enzyme_Reaction.sh" provides an example of how to do this using all 30 replicas. ### 4. Identifying the Lambda Values for the RS, TS and PS. For many of the analyses performed, we described the differences between the key stationary/saddle points along the reaction coordinate. The file "4_Example_Get_Lambda_Values.sh" provides an example of how to obtain the Lambda values corresponding to this for all 30 replicas, alongside providing an example of how to generate trajectories of each of these states for easy analysis later on. Note also the python script "q_get_extrema.py" needs to be used for this analysis (this is provided in the main folder). ### 5. Generating trajectories of the equilibration runs. An example helper script "5_Example_Equil_Trajectory_Store.sh" is provided to combine the equilibration MD simulation trajectories (those at 300 K) for each run for easier analysis (e.g. to measure things like Calpha RMSD, see section below). Note that you will need the program catdcd installed for this: https://www.ks.uiuc.edu/Development/MDTools/catdcd/ ### 6. Some example analysis scripts with CPPTRAJ. CPPTRAJ was used for the majority of the analysis performed in this paper based on the authors personal preference. Example CPPTRAJ analysis scripts to measure various properties are attached for your convenience. (the scripts themselves are commented to explain what they are doing.) These are provided in the folder "Example_CPPTRAJ_Scripts.sh" #### 7. Electrostatic Contributions calculations. To calculate the per residue group contributions (between the RS and TS) we used qtools. An example of how to do this is provided in the file: "7_Example_Get_Group_Contributions.sh