Advanced search

Message boards : News : Free ligand binding success & continuation

Sort
AuthorMessage
Profile ignasi
Forum moderator
Project administrator
Project developer
Project scientist
Avatar
Send message
Joined: Apr 10 08
Posts: 159
Credit: 5,807,978
RAC: 1
Message 17932 - Posted 12 Jul 2010 12:49:18 UTC

    Dear crunchers,
    In the past months you crunched a set of WUs that aimed at observing a free ligand binding to a protein (*IBUCH_esrever*). At least 1 of the 750 simulations has reached destination! http://youtu.be/a3IsIQiEjeQ
    Congratulations for this amazing result. However, we lack a bit of statistics for this event and we need to get more of these. We are extending the experiment (*IBUCH_freebind*). They're sitting in the queue, get yours!

    ID: 17932 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
    skgiven
    Forum moderator
    Project tester
    Volunteer tester
    Send message
    Joined: Apr 23 09
    Posts: 886
    Credit: 34,629,587
    RAC: 179,286
    Message 17942 - Posted 13 Jul 2010 12:15:46 UTC - in response to Message 17932.

      What ligand was it?

      ID: 17942 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
      Profile ignasi
      Forum moderator
      Project administrator
      Project developer
      Project scientist
      Avatar
      Send message
      Joined: Apr 10 08
      Posts: 159
      Credit: 5,807,978
      RAC: 1
      Message 17948 - Posted 14 Jul 2010 10:31:47 UTC - in response to Message 17942.

        Last modified: 14 Jul 2010 10:33:59 UTC

        The ligand is pYEEI (phosphorilated-Tyrosine, Glutamic Acid x2 and Isoleucine). It is the shortest to bind to and SH2 domain.
        We haven't performed any freeligand binding experiment of larger peptides. However we do have tryied to compute binding free energies for them: PQpYEEIPI,...

        cheers,

        ID: 17948 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
        Retvari Zoltan
        Send message
        Joined: Jan 20 09
        Posts: 44
        Credit: 10,045,906
        RAC: 173,510
        Message 17950 - Posted 14 Jul 2010 11:55:41 UTC - in response to Message 17932.

          So, these are those very long workunits.
          Give me more :)
          http://youtu.be/a3IsIQiEjeQ

          ID: 17950 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
          skgiven
          Forum moderator
          Project tester
          Volunteer tester
          Send message
          Joined: Apr 23 09
          Posts: 886
          Credit: 34,629,587
          RAC: 179,286
          Message 17953 - Posted 14 Jul 2010 13:12:41 UTC - in response to Message 17948.

            The pTyr seems to be behaving like an anchor, allowing for some serious changes in the rest of the peptide; at one stage it flips over (about 34sec). After being snapped into place it looks more at ease. Would be nice to see a big energy change at that point.

            ID: 17953 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
            Profile ignasi
            Forum moderator
            Project administrator
            Project developer
            Project scientist
            Avatar
            Send message
            Joined: Apr 10 08
            Posts: 159
            Credit: 5,807,978
            RAC: 1
            Message 17995 - Posted 16 Jul 2010 9:38:18 UTC - in response to Message 17950.

              So, these are those very long workunits.
              Give me more :)


              Nope, they are not. These are *GCY* not *freebind*.

              ID: 17995 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
              Profile ignasi
              Forum moderator
              Project administrator
              Project developer
              Project scientist
              Avatar
              Send message
              Joined: Apr 10 08
              Posts: 159
              Credit: 5,807,978
              RAC: 1
              Message 17996 - Posted 16 Jul 2010 9:43:29 UTC - in response to Message 17953.

                The pTyr seems to be behaving like an anchor, allowing for some serious changes in the rest of the peptide; at one stage it flips over (about 34sec). After being snapped into place it looks more at ease. Would be nice to see a big energy change at that point.


                Exactly.
                pTyr is the principal residue establishing the first contacts with the SH2 domain. Once it does, it doesn't detach (at the timescale we're looking at) and reduces the number of conformations that it needs to explore before binding. It is falling down to an energetic well--it likes to be there.

                cheers

                ID: 17996 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
                Retvari Zoltan
                Send message
                Joined: Jan 20 09
                Posts: 44
                Credit: 10,045,906
                RAC: 173,510
                Message 18001 - Posted 16 Jul 2010 15:58:15 UTC - in response to Message 17995.


                  Nope, they are not. These are *GCY* not *freebind*.


                  Thank you for pointing out my mistake....

                  I got a lot of *freebind* too.
                  But I like the *GCY* more, because these are more gainful in a view of the credit/time ratio :)

                  ID: 18001 | Rating: 0 | rate: Rate + / Rate - Report as offensive    
                  Post to thread

                  Message boards : News : Free ligand binding success & continuation