CCL: Docking small molecules in the binding site of metalloproteins

[Rajan Chaudhari <rchaudhari~!~mail.usp.edu>]

Hi Poonam,

Read the following article:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744578/

PLOP is free for academic use. 

Manual: http://www.jacobsonlab.org/plop_manual/plop_manual.htm ;

Autodock:

http://autodock.scripps.edu/faqs-help/faq/faqsection_view?section=Scientific%20Questions

How can I set up the protonation state of my histidine sidechains?

Histidines can be neutral or positively charged. When neutral, they can be protonated at the delta (HD1) or epsilon (HE2) positions. How can I set these up?

Using ADT

There is a command in ADT to help you decide on the protonation of the Histidines, but you have to load the commands before you can use it: go to "File > Load Module" and then scroll down, click on "repairCommands", and then click "Load Module" followed by "Dismiss". Now, go to "Edit > Hydrogens > Edit Histidine Hydrogens".

If there are any histidines in your molecule, a panel will open up listing each histidine residue along with a row of radio buttons. You can use these to choose whether each histidine should be neutral, HD1; neutral, HE2; or protonated.

Using Reduce/Molprobity

There is a very nice tool called Reduce (with a web-accessible front end called Molprobity) that can be used for adding hydrogens and optimising the hydrogen-bond network by flipping amido groups in Asn and Gln sidechains, and His imidazole rings by 180º. It can also be used for evaluating the quality of your protein structure. See:

Word, et al. (1999) "Asparagine and glutamine: using hydrogen atom contacts in the choice of sidechain amide orientation" J. Mol. Biol. 285, 1733-1745.

You need to study your receptor's active site as well as mechanism of action of binding ligand. you will get idea about protonation state of amino acids before the ligand interaction and after ligand interaction.

Hope this helps. Best Luck!

Regards,

Rajan

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From: owner-chemistry,ccl.net
To: rchaudhari,mail.usp.edu
Subject: CCL: Docking small molecules in the binding site of metalloproteins
Date: Fri, 15 Apr 2011 16:08:01 -0600

Hello

I am trying to dock some small molecules with a metalloprotein having manganese ions in its binding site.The binding site of my receptor protein comprises mostly His,Asp,and Glu residues and it is known that the presence of metal ions can alter the hydration and protonation state of these amino acid residues in the binding site.Please suggest me as how should I optimize the metal ion parameters and the protonation states of these amino acid residues in the binding site.I am using Surflex-Dock (Tripos Inc.) and Autodock for docking studies.Also, please suggest me some relevant articles in this regard.

Thank you
 





Prija Ponnan

 

Research Student

Department of Chemistry

University of Delhi

Delhi-110007, India

&

Canadian Commonwealth Scholarship Program Scholar

College of Pharmacy and Nutrition

University of Saskatchewan

Saskatoon,SKN5C9,Canada