[gmx-users] oplsaa vs. charmm

[Thomas Evangelidis]

Thank you all for your comments! Let me give you more details about my case:

I want to study the interaction modes of known inhibitors with the monomeric
state of an IDP (~100 aa). IDPs only assume secondary structure when in
complex with their partners, hence there are no crystal structures of the
protein as a monomer. The only experimental data that exist are NMR and CD
data of a close homologue (~78% sequence identity) which show that the
monomer is partially folded in the following simplified pattern:

CHHHHHHHHCCCCCCCChhHHHhhhC

where "h" denotes transient helix, "H" relative rigid helix, and "C" random
coil. The whole IDP is ~100 aa, but we have indications that the inhibitors
bind to the central disordered 40 aa. Therefore I was thinking of running
two simulations, one for the whole ~100 aa using secondary restraints
wherever applicable, and a longer one for the central 40 amino acids. The
problem with the whole-IDP simulation is that the unfolded ~100 aa will
occupy substantially bigger space than the central 40 aa, therefore the
dimensions of the box will be larger and will include much more solvent.
This will make the simulation cumbersome and I won't be able to do enough
sampling for the whole IDP.

In both simulations I am thinking of keeping the desired amino acids from
the crystal structure of the IDP in complex with its partner, carry out REMD
to unfold it, and then add an inhibitor to see where it binds.


You comments about the proposed protocol, force field and water model to
use, will be highly appreciated!

thanks,
Thomas



On 8 June 2011 22:37, Justin A. Lemkul <jalemkul at vt.edu> wrote:

>
>
> Da-Wei Li wrote:
>
>> I really don't think you can get adequate sampling for IDPs that have 40
>> residues, using full atomic MD.
>>
>>
> I disagree.  Perhaps brute force MD would not accomplish the task (unless
> you have considerable resources and don't want your answers very quickly,
> but even then...), but there are certainly a number of techniques, including
> implicit solvent, REMD, generalized Hamiltonian replica exchange, and fancy
> umbrella sampling and/or free energy settings that can vastly improve
> sampling for such systems.
>
> -Justin
>
>
>> On Wed, Jun 8, 2011 at 3:25 PM, Michael Daily <mdaily.work at gmail.com<mailto:
>> mdaily.work at gmail.com>> wrote:
>>
>>    Do you have some experimental data to compare to your IDP
>>    simulations, like X-ray scattering or some such? I'd imagine that
>>    IDP simulations with either forcefield would only be qualitatively
>>    accurate given that the forcefields are calibrated, as you say, on
>>    rigid proteins and small molecules.
>>
>>    On 6/8/11 8:00 AM, Thomas Evangelidis wrote:
>>
>>>    Dear Prof van der Spoel and GROMACS users,
>>>
>>>    I have read the article "Scrutinizing Molecular Mechanics Force
>>>    Fields..." where it is demonstrated that AMBER99sb yields protein
>>>    conformations that are in better agreement with residual dipolar
>>>    coupling, J-coupling and NOE data, compared with other force
>>>    fields. However, both proteins used for this benchmark study
>>>    (ubiquitin and protein G) are rather rigid, so I was wondering if
>>>    there is a similar analysis for flexible proteins/peptides. I want
>>>    to simulate a few intrinsically disordered proteins/peptides of
>>>    length between 40 and 100 aa and would like to know what would be
>>>    the best choice of force field to use. Any experience or knowledge
>>>    on this matter would be greatly appreciated!
>>>
>>>    thanks in advance,
>>>    Thomas
>>>
>>>
>>>
>>>    On 27 May 2011 19:01, David van der Spoel <spoel at xray.bmc.uu.se
>>>    <mailto:spoel at xray.bmc.uu.se>> wrote:
>>>
>>>        On 2011-05-27 17.50, simon sham wrote:
>>>
>>>            Hi,
>>>            I have recently done two simulations on a protein at high
>>>            temperature
>>>            near its melting temperature. At the beginning I used
>>>            CHARMM forcefield,
>>>            and then OPLSAA to double check the results. There are
>>>            some differences
>>>            in the structures between the forcefield used. I know
>>>            different
>>>            forcefields can give different results. All parameters in the
>>>            simulations were the same except the forcefield. Is there
>>>            anyway I can
>>>            tell which forcefield gives more reliable results?
>>>
>>>            Thanks for the insights,
>>>
>>>            Simon
>>>
>>>        You might want to check
>>>
>>>        Oliver Lange, David van der Spoel and Bert de Groot:
>>>        Scrutinizing Molecular Mechanics Force Fields on the
>>>        Microsecond Timescale With NMR Data Biophys. J. 99 pp. 647-655
>>>        (2010)
>>>
>>>        where we compare a number of FFs to NMR data.
>>>
>>>
>>
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