Nancy wrote:
High-throughput "in silico" screening (e.g. for ligand-protein binding) has been performed on a number of systems. How are such automated simulations performed (I assume they utilize molecular dynamics)?


I doubt that large classes of ligands have been done effectively with MD. Docking is better suited to finding initial bound configurations, after which MD can be useful in analyzing interactions over time.

Assumptions can be cleared up by reading Methods sections. If anyone has a method for using unbiased MD to demonstrate ligand binding in large classes of ligands, I'd love to know about it.

-Justin




On Fri, Jul 31, 2009 at 5:47 PM, Justin A. Lemkul <jalem...@vt.edu <mailto:jalem...@vt.edu>> wrote:



    Nancy wrote:

        If it necessary to manually create force field parameters for
        each molecule, then how can one run a simulation involving a
        number of arbitrary molecules (e.g. a set of mono and
        disaccharides) for which there are no existing force fields?

        Do you know of any other MD software package that is capable of
        running simulations on arbitrary molecules without having to
        "piece together" a force field for each molecule?


    Indeed it would be nice if there was a software package that would
    parameterize your molecule, validate said parameters, then run a
    meaningful simulation with all the proper conditions.  Maybe it
    could even make coffee...

    All kidding aside, the answer is no.  It is the job of the user to
    generate and validate parameters when none are available.  A proper
    topology is perhaps the most important part of setting up a simulation!

    There are some methods for doing some of this in an automated
    fashion (i.e., RESP charge derivation, antechamber with GAFF, etc).
     But the hard truth comes down to one simple fact - if no parameters
    are already available, you must do that work.  It is hard, but
    necessary.  Have a look at the Gromos96 force fields; they contain
    some monosaccharide building blocks that should give you a
    reasonable starting point.

    -Justin

        Thanks,

        Nancy





        On Fri, Jul 31, 2009 at 4:53 PM, Justin A. Lemkul
        <jalem...@vt.edu <mailto:jalem...@vt.edu>
        <mailto:jalem...@vt.edu <mailto:jalem...@vt.edu>>> wrote:



           Nancy wrote:

               Hello,

               I am trying to run a MD simulation on trehalose (glucose
               disaccharide) in water.  I obtained the PDB file from the
        URL:
               http://www.rcsb.org/pdb/files/ligand/TRE_model.pdb .
         When I run
               pdb2gmx on the PDB file:

               pdb2gmx -f TRE_model.pdb -o TRE_model.gro -v

               I chose force field 5 (OPLS) from the list:

               Select the Force Field:
                0: GROMOS96 43a1 force field
                1: GROMOS96 43a2 force field (improved alkane dihedrals)
                2: GROMOS96 45a3 force field (Schuler JCC 2001 22 1205)
                3: GROMOS96 53a5 force field (JCC 2004 vol 25 pag 1656)
                4: GROMOS96 53a6 force field (JCC 2004 vol 25 pag 1656)
                5: OPLS-AA/L all-atom force field (2001 aminoacid dihedrals)
                6: [DEPRECATED] Gromacs force field (see manual)
                7: [DEPRECATED] Gromacs force field with hydrogens for NMR
                8: Encad all-atom force field, using scaled-down vacuum
        charges
                9: Encad all-atom force field, using full solvent charges

               And I received the following error message:

               -------------------------------------------------------
               Program pdb2gmx, VERSION 4.0.5
               Source code file: pdb2gmx.c, line: 429

               Fatal error:
               Atom C1 in residue TRP 1 not found in rtp entry with 24 atoms
                           while sorting atoms
               -------------------------------------------------------


           Well, pdb2gmx thinks that TRE is tryptophan, so it's looking to
           complete a TRP building block.  Furthermore, your procedure is
           undoubtedly going to fail. Force fields and pdb2gmx are not
        magic;
           they are not equipped to handle any arbitrary molecule you
        may want
           to simulate.  None of the force fields provided with Gromacs will
           contain information for trehalose by default.  There is
        information
           for glucose in some of the force fields (check the .rtp
        files), and
           you may be able to piece trehalose together from that
        information.

           Otherwise, you will have to go through the *very difficult and
           time-consuming* process of parameterization:

           http://oldwiki.gromacs.org/index.php/Parameterization

           -Justin

               Please help.


               Thank you,

               Nancy







------------------------------------------------------------------------

               _______________________________________________
               gmx-users mailing list    gmx-users@gromacs.org
        <mailto:gmx-users@gromacs.org>
               <mailto:gmx-users@gromacs.org <mailto:gmx-users@gromacs.org>>

               http://lists.gromacs.org/mailman/listinfo/gmx-users
               Please search the archive at http://www.gromacs.org/search
               before posting!
               Please don't post (un)subscribe requests to the list. Use the
               www interface or send it to gmx-users-requ...@gromacs.org
        <mailto:gmx-users-requ...@gromacs.org>
               <mailto:gmx-users-requ...@gromacs.org
        <mailto:gmx-users-requ...@gromacs.org>>.

               Can't post? Read
        http://www.gromacs.org/mailing_lists/users.php


           --    ========================================

           Justin A. Lemkul
           Ph.D. Candidate
           ICTAS Doctoral Scholar
           Department of Biochemistry
           Virginia Tech
           Blacksburg, VA
           jalemkul[at]vt.edu <http://vt.edu> <http://vt.edu> | (540)
        231-9080

           http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

           ========================================
           _______________________________________________
           gmx-users mailing list    gmx-users@gromacs.org
        <mailto:gmx-users@gromacs.org>
           <mailto:gmx-users@gromacs.org <mailto:gmx-users@gromacs.org>>

           http://lists.gromacs.org/mailman/listinfo/gmx-users
           Please search the archive at http://www.gromacs.org/search before
           posting!
           Please don't post (un)subscribe requests to the list. Use the www
           interface or send it to gmx-users-requ...@gromacs.org
        <mailto:gmx-users-requ...@gromacs.org>
           <mailto:gmx-users-requ...@gromacs.org
        <mailto:gmx-users-requ...@gromacs.org>>.

           Can't post? Read http://www.gromacs.org/mailing_lists/users.php



        ------------------------------------------------------------------------

        _______________________________________________
        gmx-users mailing list    gmx-users@gromacs.org
        <mailto:gmx-users@gromacs.org>
        http://lists.gromacs.org/mailman/listinfo/gmx-users
        Please search the archive at http://www.gromacs.org/search
        before posting!
        Please don't post (un)subscribe requests to the list. Use the
        www interface or send it to gmx-users-requ...@gromacs.org
        <mailto:gmx-users-requ...@gromacs.org>.
        Can't post? Read http://www.gromacs.org/mailing_lists/users.php


-- ========================================

    Justin A. Lemkul
    Ph.D. Candidate
    ICTAS Doctoral Scholar
    Department of Biochemistry
    Virginia Tech
    Blacksburg, VA
    jalemkul[at]vt.edu <http://vt.edu> | (540) 231-9080
    http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

    ========================================
    _______________________________________________
    gmx-users mailing list    gmx-users@gromacs.org
    <mailto:gmx-users@gromacs.org>
    http://lists.gromacs.org/mailman/listinfo/gmx-users
    Please search the archive at http://www.gromacs.org/search before
    posting!
    Please don't post (un)subscribe requests to the list. Use the www
    interface or send it to gmx-users-requ...@gromacs.org
    <mailto:gmx-users-requ...@gromacs.org>.
    Can't post? Read http://www.gromacs.org/mailing_lists/users.php



------------------------------------------------------------------------

_______________________________________________
gmx-users mailing list    gmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at http://www.gromacs.org/search before posting!
Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/mailing_lists/users.php

--
========================================

Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

========================================
_______________________________________________
gmx-users mailing list    gmx-users@gromacs.org
http://lists.gromacs.org/mailman/listinfo/gmx-users
Please search the archive at http://www.gromacs.org/search before posting!
Please don't post (un)subscribe requests to the list. Use the www interface or send it to gmx-users-requ...@gromacs.org.
Can't post? Read http://www.gromacs.org/mailing_lists/users.php

Reply via email to