VMD-L Mailing List

From: WT Ren (renerwei_at_gmail.com)
Date: Thu Jul 11 2019 - 11:00:57 CDT

Dear Mariano:

Thanks very much for your valuable explanation. I will try the geometry
optimization & charge optimization with more accurate QM method.
There are a few more questions. I used the cgenff server to generate the
force field of my ligand previously. I found that the acyl phosphate group
have very hight penalties(charge~40, dihedral~160) whereas the penalties of
the left part are OK. So can I fix the charges of the low-penalties
part and just optimize the charges of acyl phosphate? If yes, is it
necessary to do QM calculation of atoms with fixed charge?
One more question is about the advanced setting of QM/MM optimization. Is
the default setting (scale of QM energy=1.16, weight of distance=1.0 ...)
proper to this highly charged ligand?

Best regards
Weitong Ren

On Wed, Jul 10, 2019 at 7:57 AM mariano spivak <mariano_at_ks.uiuc.edu> wrote:

> Hi again,
>
> I tested the set up and the calculations and this is my take on your issue.
>
> The ligand that you want to parametrize is highly charged (-4), which I
> believe is causing the water interaction issues. Some of the files are
> completely wrong given the clashes between the probe water and phophate
> (DON-H2 for example) and I don't think you can use those results. On the
> other hand, files where the probe water is repelled by the ligand are most
> likely caused by the large electrostatic interaction between the phosphate
> groups. I have not tried, but it is possible that using a "better" QM
> method for these water interaction files would solve this problem. For
> example, in the problematic gau file (DON-H3), replace HF by B3LYP.
>
> If that doesn't work, I would suggest you try the RESP fitting method and
> compare with the charge values of the standard chemical groups in CGenFF.
>
> As a side point, I played around with the ligand and found a lower energy
> structure than the one you are using in the optimized pdb. The "new"
> minimum is actually not entirely linear but forming a intramolecular
> hydrogen bond between the OH and the PO4, which results in a 7 member ring
> connecting atoms 12 (H) and 7 (O). If you are curious you might want to
> test this.
>
> Best
>
> Mariano Spivak, Ph.D.
>
> Theoretical and Computational Biophysics Group
>
> Beckman Institute, University of Illinois.
>
> mariano_at_ks.uiuc.edu
>
> mspivak_at_illinois.edu
>
>
> On Sun, Jul 7, 2019 at 11:18 AM WT Ren <renerwei_at_gmail.com> wrote:
>
>> Dear Mariano:
>>
>> Thanks very much for your reply. I uploaded the files to google drive.
>>
>> https://drive.google.com/file/d/1bGNKnq9TMh4pXSHEQNADTiPM6emeT5mT/view?usp=sharing
>> The initial PDB structure was constructed by Molefacture.
>> Now I'm confused about which QM log files should be used and how to
>> decide the proper scale parameter and the weight of distance/dipole.
>>
>> Thanks in advance!
>>
>> Best regards
>> Weitong Ren
>>
>>
>> On Mon, Jul 1, 2019 at 1:01 AM mariano spivak <mariano_at_ks.uiuc.edu>
>> wrote:
>>
>>> Hi,
>>>
>>> I can check your files to see what is the problem. You can send me the
>>> files in a separate email.
>>> It sounds like you are including water molecules from your pdb/xray
>>> structure in the FFTK framework, which is not needed.
>>>
>>> Best
>>>
>>> Mariano Spivak, Ph.D.
>>>
>>> Theoretical and Computational Biophysics Group
>>>
>>> Beckman Institute, University of Illinois.
>>>
>>> mariano_at_ks.uiuc.edu
>>>
>>> mspivak_at_illinois.edu
>>>
>>> On Sun, Jun 30, 2019 at 10:06 AM WT Ren <renerwei_at_gmail.com> wrote:
>>>
>>>> Dear All:
>>>>
>>>> I have been struggling to optimize the partial charges of one small
>>>> molecule obtained from CHARMM-GUI by fftk and gaussian for several days. I
>>>> followed the workflow in the tutorial, but unfortunately, the MM/QM
>>>> distances and energies did not converge. Some water molecules moved far
>>>> from the interaction site. I tried excluding those water molecules from the
>>>> optimization, then other water molecules would move away. It seems there
>>>> are some tricks in the charge optimization. Could anyone give me some
>>>> advice or tips on this issue. I will be very grateful for any guidance. I
>>>> can send the files if they would help.
>>>>
>>>> PS: The ligand molecule includes two phosphates and carries -4 charges.
>>>>
>>>