Dear Prof. Krueger,
Thanks for your suggestions. Indeed, I’ve been using HF/6-31G(d) for the ESP calculation since I will be using this ligand with the ff14SB forcefield.
I think I’ll go with using the low energy conformers and try to set up the weighting factors to the ratio in population %, calculated from the energy differences using Boltzmann’s formula.
Thanks for taking the time to answer,
Juan
> On 6 Jun 2017, at 12:57, Brent Krueger <kruegerb.hope.edu> wrote:
>
> Juan,
>
> I have also tried to use the weighting factors in RESP fitting, but have
> not carefully tested them in any way other than setting different
> conformers to equal (or pretty similar) weights. In principle, one would
> use the relative energies to determine Boltzmann factors which could become
> your weights. My belief is that the weighting factors you put into the RESP
> input file get normalized by RESP, so you can make the values whatever you
> like as long as their relative sizes are appropriate.
>
> In reality I think that determining these weighting factors is pretty
> difficult. One should really have free energies (rather than just
> energies/enthalpies) including an environment that represents the average
> that your residue will see in your simulations. In the standard protocol
> one uses the cheap HF/6-31G(d) in vacuum method for determining ESPs
> because the errors in this method lead to charges that are polarized in a
> way that is approximately correct for water solvation. If you will be using
> your residue with Cornell et al. type residues (e.g. ff94, ff99, ff99SB,
> ff14SB) then it is critical that you use this same approximate method
> because it is more important that your charges be balanced relative to
> those FFs than that your charges represent 'reality' for that residue.
>
> Anyway, you can certainly do some quick testing using different weights to
> see how much impact they have on the final charges. I would personally use
> just those conformers with low energies (as you mentioned).
>
> I never use R.E.D. myself, so I can't offer any help with that.
>
>
> Good luck!
>
>
> Cheers,
> Brent
>
>
>
> On Tue, Jun 6, 2017 at 7:05 AM, Eiros Zamora, Juan <
> j.eiros-zamora14.imperial.ac.uk> wrote:
>
>> Dear Amber experts,
>>
>> I am on the process of deriving point charges for a small molecule of 51
>> atoms. From is SMILES string, I’ve generated several conformers using RDKit
>> (http://www.rdkit.org/). My objective is to do multi-conformational RESP
>> fitting. I’ve seen on the Advanced Tutorial1 http://ambermd.org/tutorials/
>> advanced/tutorial1/section1.htm that the recommended way to do this for
>> reproducibility is using the R.E.D server. However I decided to manually do
>> it myself too to better understand the process.
>>
>> Starting from 9 conformers, I’ve noticed that some of them are differ in
>> energies (between 3 to 10 kcal/mol to the lowest energy conformer, Gaussian
>> SPE calculation and M06/cc-pvdz). Should I only use for resp the conformers
>> that are around < 2kcal/mol to the lowest energy conformer? I think this
>> can be also done by tweaking with the weighting factor for the
>> multi-molecule fit. But in the tutorial, it just states that is set to 1.0
>> for both conformers since the two have to be weighted equally. I’ve been
>> looking in the manual and haven’t seen much being discussed about this
>> weighting factor. Does anyone know how to use it to better represent the
>> energy difference between the conformers?
>>
>> Additionally, and this is related to the R.E.D server: is it possible to
>> modify these weighting factors according to the energy difference between
>> the conformers (after optimization, presumably)? I’ve set up a job with 9
>> conformers of the molecule in a single PDB file, but upon inspection of the
>> job results, I’ve observed that these weighting factors are all set to 1.0.
>> I’ve also noticed that the input file for resp in the R.E.D server doesn’t
>> set the nmol keyword to however many conformers there are – instead, on top
>> of every molecule section something like this is set: MOLECULE-1 nconf=1
>> norient=1 nmep=1/18 (the nconf, norient and nmep values change). Can anyone
>> comment or point me in the right direction to better understand the input
>> files for resp? I’m also a bit confused by the fact that there are 18
>> entries in this resp input file when I only loaded 9 conformers.
>>
>> Thanks for any suggestions!
>>
>> Juan Eiros
>>
>> [Imperial College London] <http://www.icb-cdt.co.uk/>
>>
>>
>> Juan Eiros Zamora / PhD Student
>> je714.ic.ac.uk<mailto:je714.ic.ac.uk> / +44 (0) 7783018326
>>
>> Imperial College London
>> Imperial College Road SW7 2AZ | UK
>> http://www.icb-cdt.co.uk/
>>
>>
>>
>>
>>
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>>
>
>
>
> --
> _______________________________________________
> Brent P. Krueger.....................phone: 616 395 7629
> Professor.................................fax: 616 395 7118
> Hope College..........................Schaap Hall 2120
> Department of Chemistry
> Holland, MI 49423
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Received on Tue Jun 06 2017 - 07:30:03 PDT
