Dear AMBER users,
I am performing thermodynamic integration for the disappearing of few ions in protein complex.
I am using Sander to convert an ion (initial state) to a dummy atom (final state).
Initially, I create a lib file for the initial state. Then change the atom name of the ion to DN (Dummy atom) and charge to 0 in the .lib file to use as final state. I also load an .frcmod file to define the DN atom type with 0 non-bonded parameters.
I am modifying both the charge and vdw parameters at the same time to make the ion disappear.
I am following the tutorial in the below link as a starting point.
http://www.rosswalker.co.uk/tutorials/psc_workshop/Tutorial_seven/
Since an ion disappears in the perturbed state, I am also using klambda=4.
I have tried with 3 clambda points as well as 9 points using the lambda and weight values given in amber tutorial.
As an example, I have shown the dv/dl averages for both 3 point and 9 point simulations.
charge+vdw; 3-point integral
deltaG of ligand in water
(154.3493*0.27777)+(92.5205*0.44444)+(28.6495*0.27777)
91.951387696
deltaG of complex in water
(162.1025*0.27777)+(115.3253*0.44444)+(46.1965*0.27777)
109.114389562
deltadeltaG=deltaGcomp-deltaGlig
17.163001866
charge + vdW perturbation 9 point integral
deltaG of ligand in water
(173.5368*0.04064)+(162.0287*0.09032)+(143.6997*0.13031)+(119.1542*0.15617)+(92.7112*0.16512)+(64.9622*0.15617)+(40.2767*0.13031)+(22.7675*0.09032)+(0.3334*0.04064)
91.792773928
deltaG of complex in water
(177.4860*0.04064)+(179.4916*0.09032)+(157.9280*0.13031)+(138.5222*0.15617)+(113.0255*0.16512)+(80.1116*0.15617)+(60.2231*0.13031)+(38.9880*0.09032)+(-6.7603*0.04064)
107.905450867
deltadeltaG=deltaGcomp-deltaGlig
16.112676939/
deltaG of ligand in water (klambda 4)
(621.0709*0.04064)+(391.0648*0.09032)+(165.8701*0.13031)+(45.9019*0.15617)+(8.6732*0.16512)+(-0.5524*0.15617)+(-2.3720*0.13031)+(-2.0549*0.09032)+(-1.0472*0.04064)
90.152924946
deltaG of complex in water (klambda 4) with restraints
(626.9129*0.04064)+(488.8959*0.09032)+(266.8167*0.13031)+(117.8476*0.15617)+(37.3120*0.16512)+(9.5520*0.15617)+(1.9104*0.13031)+(0.1281*0.09032)+(0.0008*0.04064)
130.721201821
deltadeltaG=deltaGcomp-deltaGlig
40.568276875
The use of klambda=4 makes a huge difference in the obtained deltadeltaG.
When I check the elec and vdw energies, the elec energies contribute almost entirely to the dv/dl (ex. dv/dl=470.0083; elec=488.4165; vdw=-18.4082).
This is understandable because, the ion-protein interaction is majorly electrostatic.
Also, even with a restraint weight of 10, the ions move from their initial positions and so the energies may not be reliable.
How do I decide the number of clambdas required for my system. My system is relatively small (~700 atoms) and highly charged (~-20).
How do I handle the ion movement. Position restraints doesnt seem to work.
Any suggestions and pointers regarding this would be very helpful.
Thanks in advance.
Muthukumaran Rajagopalan
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Received on Wed Jan 31 2018 - 05:30:03 PST
