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All,

Thank you for your help.
I have run the outlined computations using the suggested parameter
substitution for two molecules of interest (1,6-Ac2-alpha/beta-D-glucose)
and found the average absolute error to be 0.85 kcal/mol and 1.53 kcal/mol
(9.6% and 19.9% relative to maximum barrier height respectively). I can
share the exact results if there is any interest in this. The main
deviation lays in the region between 0-120°, where MM energies overestimate
for alpha, while underestimating for beta - making further parameterization
tricky, as I understand it.

Comparing the results for the O5-C1-O1-C1A torsion above to the rotational
energy profile for the C5-C6-O6-C1A torsion in 6-Ac-b-D-Glc (using the
existing GLYCAM parameters), where I found 0.92 kcal/mol and 6.8%
respectively, I think the parameter substitution for 1-Ac may not be ideal,
but might be sufficient to use non the less?

 -Sven

On Wed, Sep 21, 2016 at 10:07 AM, Rob Woods <[log in to unmask]> wrote:

> Hi Sven,
> 1) Do not include water (explicit or implicit) in the MM calc. You are
> trying to match vacuum QM data. Later in MD you will include water.
>
> 2) I would set R2=R3=angle.
>
> 3) Monitor the RMSD between the minimized MM and QM structures at each
> angle and make sure they are essentially the same.
>
> Good luck,
> Rob
>
> Excuse the brevity, sent from iPhone
>
> On Sep 21, 2016, at 12:28 PM, Sven Hackbusch <[log in to unmask]
> <[log in to unmask]>> wrote:
>
> Thank you to everyone that has chimed in with your help!
>
> I do have some follow-up questions about the MM energy minimization with
> the targeted torsion restrained:
>
> 1. I assume that the minimizations are run in explicit solvent (TIP3P
> model) - is this correct?
> 2. With what values do you restrain the torsion angle in your
> minimizations? In my first attempt, I kept to the AMBER tutorial 4 by
> setting r1 = angle - 2°, r2 = angle - 1°, r3 = angle + 1°, r4 = angle + 2°
>  and rk2 = rk3 = 32.0, however this seems arbitrary to me and I did not
> find anything given in the GLYCAM06 publication.
>
> Thank you!
>   -Sven
>
> On Sun, Sep 18, 2016 at 3:43 PM, Rob Woods <[log in to unmask]>
> wrote:
>
>> Hi Sven,
>> To answer your specific question, yes, we normally would develop them
>> using small representative training molecules. I would not expect there to
>> be a torsion term required for the H2. My rule is that if it is small, it's
>> preferable to use zero. But that is system dependent.
>>
>> Please remember to fit the charges with the aliphatic Hs constrained to
>> have zero net charge.
>>
>> Good luck!
>> Rob
>>
>> Excuse the brevity, sent from iPhone
>>
>> On Sep 18, 2016, at 11:50 AM, Xiaocong Wang <[log in to unmask] <[log in to unmask]>>
>> wrote:
>>
>> Hi Sven,
>>
>>
>> To develop torsion terms for missing terms in GLYCAM06, you will need to
>> generate QM energy profile for that specific torsion.  To do that, optimize
>> the molecule with that torsion restrained in QM (HF/6-31G*), then single
>> point energy calculation with the optimized structure (B3LYP/6-31G*).  We
>> usually vary the torsion angle every 30 degrees.
>>
>>
>> Once we have QM optimized structures (targeted torsion restrained),
>> perform MM energy minimization with targeted torsion restrained as well.
>> For parameters you use in MM energy minimization, set V terms for that
>> specific torsion to 0.  You will have the MM energies without rotational
>> energy corrections ("torsion energies").  The differences between QM and MM
>> (without rotational energy corrections) energies are what "torsion
>> energies" are supposed to be.  Then, develop V terms to make sure
>> rotational energies (sum from cosine functions) match the previous energy
>> differences.
>>
>>
>> It is not complicated, but it will take some time.  The logic behind
>> torsion terms development is that torsion terms (rotational energies) are
>> corrections in MM energy calculations.  Therefore, if the similar terms are
>> fairly small, it means you could either copy from similar terms or set the
>> V terms to 0.  Besides finding similar terms in GLYCAM06, you can also
>> search similar ones in parm and gaff, which are available in AMBER.
>>
>>
>> Best,
>>
>>
>> Xiaocong Wang
>> Complex Carbohydrate Research Center
>> The University of Georgia
>> 315 Riverbend Road,
>> Athens, GA, 30602
>> Tel: (706) 254-7958
>> E-mail: [log in to unmask]
>> ------------------------------
>> *From:* Users of GLYCAM & GLYCAM-Web <[log in to unmask]
>> <[log in to unmask]>> on behalf of Sven Hackbusch <
>> [log in to unmask] <[log in to unmask]>>
>> *Sent:* Friday, September 16, 2016 3:09:18 PM
>> *To:* [log in to unmask] <[log in to unmask]>
>> *Subject:* Re: GLYCAM parameters for 1-Acetylated sugars
>>
>> Hello Yohanna,
>>
>> Thank you for your offer to help!
>>
>> I think I will first try to use the approximation you recommend and
>> compare the results to QM computations to verify it is a good enough
>> approximation.
>> If I understand the Glycam06 paper correctly, I will need to generate a
>> rotational energy curve for the rotation about the Cg-Os bond for my
>> molecule at the B3LYP/6-31++G(2d,2p)//HF/6-31G* level of theory and then
>> to compare this curve to the GLYCAM06 result.
>> --Can you explain how I generate the rotational energy curve from the
>> GLYCAM06 parameters?
>>
>> If I were to have to develop my own parameters, would it be correct to
>> use two simple compounds (methyl methoxyacetate and
>> tetrahydro-2H-pyran-2-yl acetate) as a training set to generate the
>> parameters?
>> Here, I am not completely clear on how the fitting of the parameter terms
>> was performed (in terms of the math involved) and how the rotational energy
>> curve was divided into the respective atomic sequences (as opposed to using
>> just a single atomic sequence in GLYCAM93).
>>
>> Thank you again!
>>   -Sven
>>
>> On Fri, Sep 16, 2016 at 7:17 AM, Yohanna White <[log in to unmask]>
>> wrote:
>>
>>> Hello Sven,
>>>
>>> You have several options for this case. You can either make
>>> approximations and make a guess on the torsion terms, develop your own
>>> parameters, or we can develop the parameters for you and guide you through
>>> it (but this will take us about 6 weeks to get to).
>>>
>>> So if you'd like to make some approximations, you could set  the
>>> Os-Cg-Os-C to the same term as a Cg-Cg-Os-C, assuming that if this were a
>>> hexane, its torsion term would be similar. And you can set the H2-Cg-Os-C
>>> to 0 so it won't have a torsion term.
>>>
>>> Let us know if which plan works best for you.
>>>
>>> Thanks,
>>> Yohanna
>>>
>>> On Tue, Sep 13, 2016 at 9:30 PM, Sven Hackbusch <
>>> [log in to unmask]> wrote:
>>>
>>>> Dear GLYCAM developers and users,
>>>>
>>>> I am interested in simulating a sugar that is acetylated at the 1
>>>> position, specifically 1,6-Ac2-alpha-D-Glc, with the GLYCAM forcefield in
>>>> Amber.
>>>> It would appear that there exist no partial charges for this compound
>>>> (the online builder did not let me place an acetyl derivative at position
>>>> 1), so I am using the general protocol for deriving the partial charges.
>>>> However, in generating the prmtop file using xleap I am encountering
>>>> the following errors:
>>>>
>>>>  ** No torsion terms for Os-Cg-Os-C
>>>>  ** No torsion terms for H2-Cg-Os-C
>>>>
>>>> Presumably, GLYCAM is missing the dihedral angle parameters for the
>>>> O5-C1-O1-C(acetyl) and H1-C1-O1-C(acetyl) dihedral angles.
>>>>
>>>> Can anyone advise a way to overcome this roadblock?
>>>> Thank you very much for your help!
>>>>
>>>>   -Sven
>>>>
>>>>
>>>> --
>>>>
>>>> Sven Hackbusch
>>>> PhD Candidate
>>>> Department of Chemistry
>>>> University of the Pacific
>>>>
>>>>
>>>
>>
>>
>> --
>>
>> Sven Hackbusch
>> PhD Candidate
>> Department of Chemistry
>> University of the Pacific
>>
>>  <https://www.linkedin.com/pub/sven-hackbusch/53/639/aa8>
>>
>>
>
>
> --
>
> Sven Hackbusch
> PhD Candidate
> Department of Chemistry
> University of the Pacific
>
>  <https://www.linkedin.com/pub/sven-hackbusch/53/639/aa8>
>
>


-- 

Sven Hackbusch
PhD Candidate
Department of Chemistry
University of the Pacific

 <https://www.linkedin.com/pub/sven-hackbusch/53/639/aa8>