the calculation of transitions between ligands with different total charges

[hiro0426]

Hello,

I have a question regarding the calculation of transitions between ligands with different total charges.

As per the tutorial, I've followed the steps to prepare equilibrium simulation files for each end-point using ligandhybrid. However, I've encountered an issue where the net charge is not 0 during the production run, and I anticipate charge changes during the transition path as well.

Could you please provide guidance on how to set up the system appropriately to address this?

Thank you in advance for your assistance.

[zetadin]

Hi.

One can use the double-system/single-box method, where you have two copies of the hybrid ligand in the simulation box but at opposite states. Eg. first one in the binding pocket and transitioning from A to B state and the second one in the solvent simultaneously transitioning from B to A. The solvent copy should be kept far away from the protein to avoid interactions between them, eg. by using a restraint between the two and a fairly large simulation box size to also prevent interactions across the periodic boundary. See Figure 3 in doi:10.1007/978-1-4939-1465-4_9.

Cheers,
Yuriy.

[hiro0426]

Hello,

Thank you for your prompt response.

If I understand correctly, with the pmx command, I should employ "pmx double box" to create a pdb file for the complex of StateA and the ligand of StateB (the complex of StateB and the ligand of StateA). From there, I can generate a topology file.

Additionally, when applying restraints, should I use NPT run with restraints based on parameters such as the distance between ligand centers of mass?

I appreciate your further guidance on this matter.