Dear Reza,
I would back Jon’s idea of looking at homologues, although
this does depend on how close the homologue is. For example, if your protein
has a “P” loop, with the Walker A sequence motif, then I think it would be very
surprising if the nucleotide bound in different way to other P loop proteins.
However, another objective way of fitting is to look at the stereochemical
environment of the binding site. You might expect the phosphates to have
several hydrogen bonds to the protein, very possibly involving basic side
chains (Arg or Lys) and main chain amide groups. The adenine ring, on the other
hand, typically sits in a more hydrophobic pocket, often with the adenine ring
involved in a stacking interaction with a side chain.
The other objective test you can do is to try refining with different ways of
modelling the nucleotide binding and see if the 2FoFc and difference maps look
better for one binding mode than the others (and if the atomic B factors look
more sensible). The phosphate groups are significantly more electron dense than
the rest of the nucleotide. However if the density really is poor, it might be
difficult to get an unambiguous answer, in which case you might have to rely on
the stereochemical environment.
Good luck,
Andrew
> On 23 Jul 2020, at 18:12, Reza Khayat <rkha...@ccny.cuny.edu> wrote:
>
> Tried the homologues thing. There are homologues and I've done the fitting,
> but this is what I consider to be subjective. I'm certain the referee will
> ask: Given the quality of density for the nucleotide, how certain are the
> authors that a different fit is not possible? Have other fit poses been
> considered?
>
> Reza
>
> Reza Khayat, PhD
> Assistant Professor
> City College of New York
> Department of Chemistry and Biochemistry
> New York, NY 10031
> From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Jon Cooper
> <0000488a26d62010-dmarc-requ...@jiscmail.ac.uk>
> Sent: Thursday, July 23, 2020 1:07 PM
> To: CCP4BB@JISCMAIL.AC.UK
> Subject: [EXTERNAL] Re: [ccp4bb] Modeling ATP/ADP
>
> Hello, do you have any homologues in the PDB with ATP, etc, bound as a guide?
> Coot is pretty good at fitting known ligands, and unknown ones, too!
>
>
> -------- Original Message --------
> On 23 Jul 2020, 17:53, Reza Khayat < rkha...@ccny.cuny.edu> wrote:
>
> Hi,
>
> Can folks suggest programs for objectively docking ATP/ADP molecules into
> density? Our density is not so good, probably because of occupancy, and we'd
> like a less subjecting approach for modeling. Thanks.
>
> Best wishes,
> Reza
>
> Reza Khayat, PhD
> Assistant Professor
> City College of New York
> Department of Chemistry and Biochemistry
> New York, NY 10031
>
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