I’ve been trying to work out the effect of ligand binding on homodimer formation. I’m dealing with 2 X-ray structures involving the same receptor bound to two different ligands.
The ligands bind on the homodimer interface (one per subunit). The subunit main cavity is occupied by serendipitous ligands.
I performed explicit solvent MD simulations of the dimer complexes in which the serendipitous ligands were stripped. The starting coordinates and conformations of the biological ligands were as per X-ray model. I also performed two separate MD simulations (a) dimer without any ligands (serendipitous or biological) and (b) monomer without any ligands.
I used cpptraj molsurf to obtain the SASAs of the dimer interface residues. A typical example of a cpptraj input is:
parm complex_solv.prmtop
trajin prod_0-100ns.nc 1 10000 200
molsurf IntRes :71 out Val71.dat
The process was repeated for each interface residue for (1) monomer stripped of ligands; (2) dimer stripped of ligands; (3) dimer with ligand_1; (4) dimer with ligand_2
The dimer interface consists of 28 residues.
For all residues I obtained the same SASA. Typical examples are shown below.
Val71
His72
Leu73
Glu74
His77
monomer_apo
129.926556
154.186386
148.421838
142.796564
154.709454
dimer_apo
129.384386
154.215862
148.084478
143.101678
153.807794
dimer_deet
130.021954
154.398068
149.21626
143.135464
154.704514
dimer_6MH
129.644992
154.301966
149.275882
143.195312
154.090458
I find these results hard to explain unless the above input script is wrong.
Any suggestions would be most welcome
Regards
George
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Received on Wed Mar 02 2016 - 14:00:03 PST
