[gmx-users] ASN instead of ASP in the binding site: how to find the novel complex conformation ?

[Konrad Piwowarczyk]

> Dear all,
> 
> I am simulating protein dimer both without and with the ligand in the 
> binding site. The structure that I got from PDB has the ligand (a 
> molecule of ASP) in the binding site, and my goal is to simulate the 
> dynamics of the protein without the ligand and with a novel but similar 
> ligand (a molecule of ASN) that was put in the same position of the old 
> ligand but randomly oriented (in order to avoid any bias). The 
> simulation of the dimer without ligand was fine, but I have encountered 
> a big trouble during the ligand-dimer complex simulation, realising that 
> after 600-700 ps there was a separation of the two monomer, a loss in 
> sec.strucure and an almost stepwise increase of the radius of gyration 
> (also, the complex starts to rotate around an axis with great speed).
> 
> Therefore, I have two questions:
> 
> 1. Could anyone provide me an explanation for a strange event like 
> rotation ?

>From the point of view of physicist I suspect that you did not set angular momentum of the protein to be zero - in the words of gromac's *.mdp option, try to set: comm_mode=Angular and nstcomm=1 (e.g.).
The rotation that looks strange happens when energy flow between different degrees of freedom of any molecule is blocked, then energy obtained by molecule is not used for oscillation of atoms but rather appears as translational or rotational kinetic energy that must be removed externally.
The rotation may also cause separation in your molecule - just recall what happens with your hands when you swivel rapidly.

> 2. I am also thinking to use another approach to the problem, keeping 
> protein atomic positions restrained except the ones in the binding site: 
>   what do you think about it? Should I keep all the positions restrained
> ?
> 
> The simulations have been performed using pbc, cut off electrostatics, 
> GROMACS FF and with implicit solvent (these are preliminary simulations).
> 
> Thanx
> 
> LM
> 
> 
> 
> ................................................................................................
> 
> Luca Mollica
> Dulbecco Telethon Institute (Biomolecular NMR Lab)
> 
> DIBIT-HSR,Via Olgettina 58, 1B4
> 20132 Milano (Italy)
> 
> Tel: 0039-02-26434824(Office)/26433497(Lab)
> Fax: 0039-02-26434153
> E-mail: mollica.luca at hsr.it
> 
> 
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