Effects of Colored Noise in the Dynamic Motions and Conformational Exploration of Enzymes

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The present manuscript entitled by “Effects of Noise in the Molecular Simulations of Enzymes” offers solutions for non-uniform type noises and they have modified the corresponding equations to achieve to more realistic simulation. Although the employed analyses are not too deep and the used techniques are narrow in nature, I think they suffice for purposes author follow. In this respect, I recommend publication of this manuscript subject to below modifications:

- The title is too general. It should clearly points to what the authors have done, specifically.

- The authors have focused on conformational motions, while stretching and bending motions are also present. The authors should explain why they have neglected these two and how their procedure can be implemented for these two.

- I could see four distinguishable and distinct peaks in the heat-map diagram Figure 2a, but I expected other. The authors should include their expectations and discuss how this figure is different/same-as from their expectations.

- Too many important citations are missing. For example:

Noise in Biomolecular Systems: Modeling, Analysis, and Control Implications (Briat et al)

Noise-induced variability of nonlinear dynamics in 3D model of enzyme kinetics (Bashkirtseva et al)

Modeling-Based Investigation of the Effect of Noise in Cellular Systems (Gonze et al)

- In general Van der Waals is abbreviated as vdW, not VdW.

Author Response

"Please see the attachment"

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Dear authors,

The manuscript I reviewed is good, but there are several queries arisen while reading the manuscript. Here about the queries

1. In primary assumption, the TIMESCALE vs Fluctuations in Langevin equation (LE), are quite diverged. How they achieve it, A bit more detail will be beneficial in terms of conformations.

2. The other interesting is, how the GLE differs from the LE, especially in terms of kernel function K(t−τ)

3. What about the simulation box size differs impact on the noise?

4. minimization and equilibration protocols could be explained better

5. Regarding the conformational ensemble-based works, and how the effect of LE and also noise, can be discussed.

6. GLE method – Conformational space and angle variations – could you discuss?

7. While discussing RMSF and PCF, add account of RMSD and secondary structure could be more interesting
Comments on the Quality of English Language

Fine and proof readen will be okay

Author Response

"Please see the attachment"

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

See attached.

Comments for author File: Comments.pdf

Author Response

"Please see the attachment"

Author Response File: Author Response.pdf