Reviewer response for version 1
Overall comment: The article in the present form needs some revision including through checking of grammar and sentence structure. 
Further, I would request the authors to consider following points.
- Authors have written that "All bonds were constrained by LINCS". 
This claim needs to revisit. 
Generally, bonds involving hydrogen atoms are restrained using LINCS .
- Authors have mentioned that "In order to avoid the steric clashes, overall geometry and atomic charges were also optimized". 
I do not think authors have optimized the atomic charges. 
Rather atomic charges were obtained from the OPLS forcefield that was used in the simulations.
- The cutoff used for PME was 0.9 Angstrom. 
This is very small. 
It should rather be 9 Angstrom.
- Berendsen thermostat with V-rescale is not a good option for conformational sampling. 
A better option is Langevin dynamics.
- Authors have written that "The system was further energy minimized without any restraints for 50,000-time steps; the steepest descent having step size 0f 0.01 ps". 
This claim needs to revisit. 
No time-step is required for energy minimization. 
Only to study dynamics, i.e, to integrate Newton's equation of motion, we need to set time-step.
- It was not mentioned what time-step was used for the heating stage and production simulation.
- Docking is not a good method for predicting the binding free energy. 
It is the least accurate method for estimating the binding free energy. 
However, it is a very good method for predicting the binding pose. 
Authors should have conducted MM-PBSA type analysis to estimate the binding free energy.
- Figure 4 A, B, C are not required.
- Looking at Figure 4D, one can see that the for a couple of cases, longer simulation is required. 
The simulation length is too small (20 ns) to investigate the dynamics of proteins. 
They should extend all simulations to 50 ns.
- Figure 4: 
Use bigger fonts. 
It's not readable.
- Calculate average RMSD and Radius of Gyration during the simulations.
- Authors have written that "RMSF with respect to each residue....". 
RMSF is calculated with respect to the average structure obtained from simulations. 
Do you use C-alpha atoms of each residue?
Structure
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Structure
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