Distance between COM of protein and ligand along positive and negative Z axis

[Jignesh Prajapati]

Dear All,

I am trying to study how molecule passes through the porins which are proteins, present in outer membrane of bacteria and allows the transport of different chemical entities inside cell. So, one of the reaction coordinate is distance between center of mass of protein and ligand along Z axis (as protein diffusion axis is aligned with Z axis). I understood most of things from manual and plumed user groups and only problem I encountered is specifying direction of projection (positive/negative). Sometimes molecules starts to move in negative direction and sometimes in positive direction.

Here is my input file,

WHOLEMOLECULES STRIDE=1 ENTITY0=130514-130555

# this is a center of mass of ligand
a: COM ATOMS=130514-130555

# this is a center of mass of protein
b: COM ATOMS=1-5205

# this is the distance between center of mass a and b
d: DISTANCE ATOMS=a,b COMPONENTS NOPBC

METAD ARG=d.z SIGMA=2 HEIGHT=1 PACE=10 LABEL=restraint

PRINT ARG=d.z,restraint.bias STRIDE=10  FILE=COLVAR

I have played around with periodicity and other options but behavior is same. Only difference I could figure out is that putting ligand at different position, changes the behavior and It seems ligand start to move in direction where Z axis vector is long (I might be wrong).

So please suggest me the way to specify direction. Thanks in advance and appreciate your assistance.

[Giovanni Bussi]

Hi,

if I understood correctly you are surprised that the ligand sometimes goes "up" sometimes "down". This is expected. The nice feature of metadynamics is that it just disfavor the current (and past) conformations, but put no bias in principle on the way to escape from them. The system is typically allowed to take the best path, usually the one for which the thermodynamic force is slower. So, I do not think this is a problem.

A few other comments on your input:

1. Shouldn't the protein also be whole to compute its COM?

2. I do not think DISTANCE NOPBC is a good idea here. d.z will experience jumps depending on how the MD code moves the ligand between periodic images. NOPBC should only be used when two atoms are part of a whole entity (typically a single molecular made whole with the WHIOLEMOLECULES command).

3. Have a look at the example at the end of this page (http://plumed.github.io/doc-v2.0/user-doc/html/_d_i_s_t_a_n_c_e.html). You might need to use this trick if you want metadynamics to  work correctly when d.z changes sign.

Regards,

Giovanni

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[Jignesh Prajapati]

Dear Giovanni,

Thank you so much for reply.

You are correct that the initial conformation of ligand might not be in most favorable state, so we observed that initially ligand starts to move here and there. But after some steps, it will go in one direction only and as I mentioned earlier it always follows one direction either positive or negative Z direction and doesn't change through out simulation. So the question is, does it possible to control the direction of projection along Z axis?

For us it is very much important to control the direction because the proteins we generally work on are outer membrane channels presents in bacteria. So these proteins are exposed to surrounding environment and allow  transport of nutrients/antibiotics inside cell and generally reverse mechanism is not observed in this class of protein. For that different protein named efflux pumps are available which allows transport from inside to outside of cell. So, we always have to keep ligand on one side protein (which is extracellular side) and see the projection in one direction only.

Thank you so much for nice comments on input file. I will implement them in my simulations.

Regards,
-Jignesh