Assessing Molecular Dynamics in Predicting Aptamer–Ligand Binding Thermodynamics: Insights from the OTA Binding Aptamers

Files (Gromacs and Gaussian) to reproduce the data obtained in the paper: "Assessing Molecular Dynamics in Predicting Aptamer–Ligand Binding Thermodynamics: Insights from the OTA Binding Aptamers"

-----Input files for running MD simulations and analyses divided by system OBA3 (OBA3OTA, OBA3OTB and Ligand free: 5 replicas) and OBA33 (OBA33OTA, OBA33OTB and Ligand free: 5 replicas)-----

- covar.log, eigenvec.trr, eigenval.xvg: results of the covariance analysis for subsequent PCA, performed on the concatenated trajectory of the aptamer atoms of OBA3OTA (1us simulation) and the aptamer atoms of the ligand-free OBA3 (5x1μs simulations, each sampled every 5 frames). 

- covar.log, eigenvec.trr, eigenval.xvg: results of the covariance analysis for subsequent PCA, performed on the concatenated trajectory of the aptamer atoms of OBA33OTA (1us simulation) and the aptamer atoms of the ligand-free OBA33 (5x1μs simulations, each sampled every 5 frames). 

Each folder (Ligand-free, OBA3OTA, OBA3OTB, OBA33OTA, OBA33OTB) includes:

- topol.top: topology used for the MD simulation;
- Ochra_A_PhOH_DUM.itp and Ochra_B_PhOH_GMX.itp: acpype-generated topologies for OTA and OTB. For OTA, the dummy atom mimicking the chlorine σ-hole is included;
- run.mdp: mdp files for running the MD simulations;
- index.ndx: index used for MD simulations;
- eq.gro: system coordinates after the equilibration;
- md.gro: system coordinates after the 1μs production run;

- rmsd.xvg: RMSD performed on the phosphorous aptamer atoms with respect to the centroid of the models in PDB;
- rmsf.xvg: RMSF performed on the aptamer atoms with respect to the centroid of the models in PDB (OBA3 systems);
- 2dproj.xvg: projection of the trajectory of the aptamer atoms onto the first 2 principal components identified during the covariance analysis.

-----Input and output files for QM calculations with and without the chlorine dummy atom (σ-hole)(OBA3 systems)----- 

-----Input and output files for alchemical free energy calculations: 5 replicas (rep1, rep2, rep3, rep4, rep5)-----

Rep1 includes:

-launch_rep.py: python script to perform all the simulations necessary for the free energy estimation;

-top: folder with the hybrid topology;

-data_wat and data_dna: folders with the output files of the alchemical free energy calculations;

-OTA_wat, OTA_dna, OTB_wat, OTB_dna: folders containing all the files to reproduce equilibrium and non-equilibrion simulations for each system necessary to build the thermodynamic cycle).

Rep2, Rep3, Rep4 and Rep5 contain the obtained results for each replica. These results were obtained using the files in Rep1. 

OBA3 folder contains alchemical files for free energy diagnostics.