[gmx-users] Using ATB to generate valid topologies

[David van der Spoel]

On 12/07/16 13:47, Justin Lemkul wrote:
>
>
> On 7/11/16 9:52 AM, ALEXANDER DHALIWAL wrote:
>> Dear GROMACS users,
>>
>> I am pioneering the use of GROMACS in my lab to supplement some of our
>> experimental research. I have generated some topologies from the
>> Automated
>> Topology Builder (ATB), but I am unsure whether or not to trust the files
>> provided by this service. I am only an undergrad, so I would not feel
>> comfortable asking my supervisor to invest thousands of dollars into a
>> program such as Gaussian09 to validate these topologies. Does this
>
> One would not use Gaussian to validate ATB topologies.  One would
> generally *start* with a QM calculation to get charge distributions,
> then validate against other data.  The problem with the GROMOS force
> field is that there is little connection between QM calculations and the
> final topologies.  I have posted at length on this topic just within the
> last few days; please check the archive.
>
>> community trust the outputs of ATB and, if not, could you provide me with
>> suggestions as to how I may validate my topologies given my
>> restraints? Any
>> advice would be much appreciated.
>>
>
> It depends on how complex the molecules are.  GROMOS parametrization is
> empirical; existing building blocks are put together to yield a
> molecule, and any unknown groups or strange linkages are explicitly
> parametrized using model compounds.  I don't recall all the guts of what
> ATB does (I haven't used the GROMOS force field in a long time) but I
> believe it is doing this, coupled with a quick QM calculation for charge
> refinement in the case that the constituent groups are not easily looked
> up from an existing database).  In general, the topologies from ATB are
> significantly better than from, e.g. PRODRG, but the skeptic/force field
> purist in me never trusts a black box.  The problem, when it comes to
> ligands/drugs is lack of target data.  For small molecules, there are
> thermodynamic properties that one can look at.  For more complex things
> like drugs, you might get lucky and have something like a logP tabulated
> somewhere, but such data can often be difficult or impossible to obtain.
>
> -Justin
>
http://virtualchemistry.org provides validated topologies for about 150 
compounds, that is force fields have been tested by running liquid 
simulations.


-- 
David van der Spoel, Ph.D., Professor of Biology
Dept. of Cell & Molec. Biol., Uppsala University.
Box 596, 75124 Uppsala, Sweden. Phone:	+46184714205.
spoel at xray.bmc.uu.se    http://folding.bmc.uu.se