I don't think much has been done on that topic. I can tell you that it
depends strongly on the Born radii used for the atoms. We have a
manuscript in review that shows that PB overestimates Arg salt bridge
just as much as GB unless the radii are modified.
I think any implicit water model may have trouble with this unless it
is specially trained to treat Arg as compared to explicit water.
You'll need to take extra measures to compare to experimental data-
the calculations on their own will have much uncertainty as compared
to typical MM-PBSA results.
On Tue, Aug 9, 2011 at 9:59 AM, Catein Catherine <askamber23.hotmail.com> wrote:
>
> Dear Carlos,
> Thank you very much for your comments.
> Based on your experience would you believe the PBSA energy for a protein-DNA complex, given problem of basic residue and phosphates interaction? Yes, the mutation is from ARG to Ala, is PBSA able to energy difference for this type of calculations?
> Best regards,
> Catherine
>
>> From: carlos.simmerling.gmail.com
>> Date: Tue, 9 Aug 2011 07:24:22 -0400
>> To: amber.ambermd.org
>> Subject: Re: [AMBER] GBSA calculations for protein-protein complexes
>>
>> Personally, I would not trust GB calculations to give me anything
>> reliable for such a system. Protein-DNA complexes are typically
>> stabilized by interactions of basic residues with phosphates- and
>> these are known to be problematic in most GB models. You don't say
>> which residue is mutated to Ala, but if it's Arg then my feeling would
>> be not to expect much accuracy.
>>
>> Why not use PBSA for this? Are you following something in the
>> published literature where GB was shown to work well in DNA binding
>> energies? As always, you need to either follow the published
>> literature (with care, it often has weaknesses) or understand well the
>> limitations of the models. With GB, the main limitation is in exactly
>> what's important for what you are trying to study. I wouldn't use it.
>>
>> On Tue, Aug 9, 2011 at 4:04 AM, Catein Catherine <askamber23.hotmail.com> wrote:
>> >
>> > Dear Sir/Madam,
>> > In another sets of calculations, I have calculated the binding energy (GBTOT) for several protein-DNA complexes, these complexes are structurally similar with one of the interacting residues being mutated to alanine.
>> > Given the DS was not calculated, can I confidently comments on their RELATIVE GBTOT energy?
>> > What about if I want to compare the binding energy in a protein-DNA complex with a protein-protein complex? Since these two complexes are structurally dissimilar, is it a must to calculate DS for each complexes before doing doing this comparison? However, I have heard that calculating DS for large complexes are computationally demanding, and the accuracy of DS is not very high. Thus, overall, what is the common practice to get the GBSA binding energy comparison for protein-DNA and protein-protein complexes?
>> > Best regards,
>> > Catherine
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>> >
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Received on Tue Aug 09 2011 - 12:00:03 PDT
