On Sun, Oct 4, 2015 at 5:42 PM, Rahul Ramesh <raramesh.umich.edu> wrote:
> Hello Jason
> I'm trying to simulate a cellulosic molecule with a succinic group. ( This
> is my model compound as I am going to simulate a larger system in future )
> I assigned the charges using the AMBER 99SB FF. I performed Thermodynamic
> Integration of this structure and obtained a value of -25 kcal/mol. Since I
> wanted to confirm the value of this del G ref against the pKa , I performed
> a CpHMD at pH = pKa. I expected the system to be protonated/ deprotonated
> 50 % of the time. But I end up getting 100% protonation. I used the same
> set of parameters for both TI and CpHMD.
> I went through the mdout file and the EEL , EGB and 1-4 EEL are not
> convincing.
>
If you are getting 100% protonation, then your reference energies must be
wrong.
> NSTEP = 125000 TIME(PS) = 2250.000 TEMP(K) = 237.22 PRESS =
> 0.0
>
> Etot = -262.6830 EKtot = 24.2773 *EPtot =
> -286.9603*
>
> BOND = 21.5394 ANGLE = 26.4520 DIHED =
> 24.9527
>
> 1-4 NB = 6.7956 *1-4 EEL = -89.1130* VDWAALS =
> -3.9488
>
> *EELEC = -25.1198 EGB = -248.5186* RESTRAINT =
> 0.0000
>
> The electrostatic energy is positive if you subtract 1-4 EEL from EELEC.
>
Why are you subtracting them? The total electrostatic energy is the *sum*
of the two.
> I'm thinking of a reason as to why the electrostatic energy is really low
> and 1-4 EEL and EGB is really high?
>
> I compared my system (cellulosic molecule attached to a succinic group) to
> a succinic acid (COOHCH2CH2COOH) system. Basically I simulated just the
> side group of the cellulosic molecule using the AMBER99SB FF. I followed
> the same procedure as above and I was able to get 50 % protonation at pH =
> pKa and a del G ref as -22 kcal/mol ( pH = 4.2).
>
> I tried comparing the mdout file for succinic acid to the above mdout file
>
> *Protonated State for Succinic Acid*
>
> NSTEP = 999600 TIME(PS) = 3999.200 TEMP(K) = 545.62 PRESS =
> 0.0
>
> Etot = -63.8361 EKtot = 19.5165 *EPtot =
> -83.3526*
>
> BOND = 2.1652 ANGLE = 8.1213 DIHED =
> 7.6514
>
> 1-4 NB = 0.8964 *1-4 EEL = 19.4734* VDWAALS =
> -0.8920
>
> *EELEC = -93.5325 EGB = -27.2358* RESTRAINT =
> 0.0000
> *Deprotonated State for Succinic Acid*
>
> NSTEP = 999550 TIME(PS) = 3999.100 TEMP(K) = 438.95 PRESS =
> 0.0
>
> Etot = -88.1985 EKtot = 15.7011 * EPtot =
> -103.8997*
>
> BOND = 2.2672 ANGLE = 10.6449 DIHED =
> 8.7225
>
> 1-4 NB = 0.6721 *1-4 EEL = 21.5060 * VDWAALS =
> -1.0602
>
> *EELEC = -55.1840 EGB = -91.4680 *RESTRAINT =
> 0.0000
> For the Succinic Acid case , EELEC is negative and different between the
> EPtot of the protonated and deprotonated is approximately the Del G ref. I
> was expecting the same behavior for my cellulosic molecule attached to
> succinic group.
> Could you comment on the reason for EELEC being positive in the first case
> and high value of 1-4 EEL and EGB
>
EELEC can be positive, and if you have a system that carries a net charge,
you should expect that the EELEC *would* be positive (like charges repel).
EGB screens ELEC, so it is often around the same size, but opposite in
sign, of EELEC. As for the 1-4 EEL interactions -- those can be very large
if dihedrals connect atoms with large charges.
The difference in electrostatic energy between two different charge
vectors can be surprising and counterintuitive -- fixed-charge force fields
are not *intended* to have changing charges, so the free energy of changing
charges is unpredictable. That's why we have the reference energy -- to
correct for everything the force field gets "wrong".
Another, potentially easier, way of calculating reference energies is to
calculate a single-point energy difference for a typical conformation
between the two charge states and use that as a starting guess. Titrate
the model compound and then use the pKa you fit to the titration curve to
correct the reference energy (this can be done in a single step).
HTH,
Jason
--
Jason M. Swails
BioMaPS,
Rutgers University
Postdoctoral Researcher
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Sun Oct 04 2015 - 19:30:03 PDT
