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>