From: Kenno Vanommeslaeghe (kvanomme_at_rx.umaryland.edu)
Date: Tue Oct 15 2013 - 15:50:25 CDT
If the potential energy (electrostatic or otherwise) is *exactly* zero,
without fluctuations in function of simulation time, it is almost certain
the user did something terribly wrong.
Additionally, the specific quantity the user is trying to calculate
(static potential energy of binding with (implicit) vacuum reference
state) is almost always significantly negative (barring a very bad choice
of interacting residues); little or nothing can be concluded from the
absolute value.
On 10/15/2013 03:43 PM, Thomas Evangelidis wrote:
> You neglect completely the entropic effect of ligand binding:
> DeltaG=DeltaH-T*DeltaS
> Judging from your interaction energy DeltaH ~ 0 so in order to have a
> favourable Free Energy of Binding (DeltaG<0) then DeltaS>0, which means
> the removal of waters and/or ions from the binding cavity by the ligand
> increases the entropy of the system.
>
> As Aron & Kenno suggested, MM/PBSA calculations are most suitable for your
> case. FEP and TI are cumbersome and used more for ligand optimization.
>
>
> On 15 October 2013 21:43, James Starlight <jmsstarlight_at_gmail.com
> <mailto:jmsstarlight_at_gmail.com>> wrote:
>
> Aron,
>
> thanks for reference.
>
> By the way how the Namd-energy plugin could be effectively used ? In
> case of small tutorial I choce two selections- all atoms of my ligands
> and 5 polar residues surrounded ligand within the protein cavity. Than
> I calculate electrostatic energy using cutoff and switch values from
> the conf file of MD production run. In the resulting graph I've obtain
> Zero-line of the energy during of all simulation run (so if this is
> POTENTIAL energy it indicate that no interactions between ligand and
> selected residues have been occurred during MD that is incorect). What
> I did wrong?
>
> James
>
>
> 2013/10/15 Aron Broom <broomsday_at_gmail.com <mailto:broomsday_at_gmail.com>>
>
> there was in fact one recently posted on the NAMD website and
> mentioned on the mailing list.
>
>
> On Tue, Oct 15, 2013 at 1:42 PM, James Starlight
> <jmsstarlight_at_gmail.com <mailto:jmsstarlight_at_gmail.com>> wrote:
>
> So in that case just ussage of VMD's NAMD energy module would
> give wrong results of the G-bonding estimation.
> Also I've found that Free energy perturbation and
> Thermodynamic integration could be usefull for affinity
> measurements. I've seen tutorials for implementation of such
> methods for gromacs and charm but is there any for NAMD?
>
> James
>
>
> 2013/10/15 Aron Broom <broomsday_at_gmail.com
> <mailto:broomsday_at_gmail.com>>
>
> As an FYI, that energy is going to be border-line useless
> without having an unbound control to subtract.
>
> You may want to read up on the literature surrounding
> this, it is a very large topic, with many nice reviews,
> and the problem itself is fairly nuanced. What you seem
> to be talking about is an MM/PBSA style of calculation, so
> I'd start by looking into that.
>
>
> On Mon, Oct 14, 2013 at 2:20 PM, James Starlight
> <jmsstarlight_at_gmail.com <mailto:jmsstarlight_at_gmail.com>>
> wrote:
>
> Dear NAMD users,
>
>
> I have trajectory of the protein complexed with the
> ligand (burried in the protrein interiour from the
> start of simulation). Now I want to find out how I can
> calculate affinity of my ligand to the protein. The
> one possible way of do such task is the interaction
> energy estimation of my complex (based on the
> occurence of the non-covalent contacts between both
> partners during production run). Could someone provide
> me with some tutorial or explain me how I could
> perform such analysis with the VMD tools ?
>
> Thanks for help,
>
> James
>
>
>
>
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo
>
>
>
>
>
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo
>
>
>
>
>
> --
>
> ======================================================================
>
> Thomas Evangelidis
>
> PhD student
>
> University of Athens
> Faculty of Pharmacy
> Department of Pharmaceutical Chemistry
> Panepistimioupoli-Zografou
> 157 71 Athens
> GREECE
>
> email: tevang_at_pharm.uoa.gr <mailto:tevang_at_pharm.uoa.gr>
>
> tevang3_at_gmail.com <mailto:tevang3_at_gmail.com>
>
>
> website: https://sites.google.com/site/thomasevangelidishomepage/
>
>
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