Dear Niel,
thanks a lot for the answer, I will look into the links you send me. It
looks very interesting!
Best,
Andreas
On 01/23/2017 08:51 PM, Niel Henriksen wrote:
> Hi Andreas,
>
> In my opinion, the difference between Woo and Roux's approach and the other
> one you mentioned ("difference between the [PMF] curve's energy minimum and
> the value at the maximum distance") is that the former is rigorously valid,
> whereas the latter may have significant errors depending on the specific
> receptor/ligand and the restraints involved.
>
> When some sort of biasing restraint is used to compute a free energy, you
> should always be certain that the entire free energy pathway is
> considered. In the simplest case, let's imagine that I use a single
> distance restraint between a ligand and the receptor to move the ligand out
> of the binding pocket over a series of sampling windows. To be rigorously
> correct, I should first compute the work (aka free energy) of attaching the
> distance restraint between the ligand and receptor, and then the work to
> move the ligand away from the receptor, and finally (if I need to compare
> with experiment), the work to place the ligand at standard concentration (1
> M). In some cases, the work of attaching the restraint will be small and
> possibly negligible, but I would make that assumption very carefully.
>
> We have been developing an approach in the Gilson lab called
> Attach-Pull-Release which is a similar in flavor to Woo and Roux's
> approach. See this paper
> <http://pubs.acs.org/doi/abs/10.1021/acs.jctc.5b00405> and a recent tutorial
> <http://ambermd.org/tutorials/advanced/tutorial29/> for more info.
>
> Best,
> --Niel
>
> On Mon, Jan 23, 2017 at 9:03 AM, Andreas Tosstorff <
> andreas.tosstorff.cup.uni-muenchen.de> wrote:
>
>> Hi all,
>>
>> I saw different approaches on how to calculate free binding energies
>> from PMFs in the literature:
>>
>> For example in Woo and Roux Paper from 2005, called "Calculation of
>> absolute protein–ligand binding free
>> energy from computer simulations" they used a set of equations to
>> calculate different contributions to the total free energy.
>>
>> Some took the difference between the PMF curve's energy minimum and the
>> value at the maximum distance.
>>
>>
>> So what's the best approach to calculate free energy of binding from a PMF?
>>
>>
>> Kind regards,
>>
>>
>> Andreas
>>
>> --
>> M.Sc. Andreas Tosstorff
>> Lehrstuhl für Pharmazeutische Technologie und Biopharmazie
>> Department Pharmazie
>> LMU München
>> Butenandtstr. 5-13 ( Haus B)
>> 81377 München
>> Germany
>> Tel.: +49 89 2180 77059
>>
>>
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--
M.Sc. Andreas Tosstorff
Lehrstuhl für Pharmazeutische Technologie und Biopharmazie
Department Pharmazie
LMU München
Butenandtstr. 5-13 ( Haus B)
81377 München
Germany
Tel.: +49 89 2180 77059
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Received on Tue Jan 24 2017 - 01:00:02 PST
