From owner-chemistry@ccl.net Sat Apr 16 13:31:00 2011 From: "Rajan Chaudhari rchaudhari-,-mail.usp.edu" To: CCL Subject: CCL: Docking small molecules in the binding site of metalloproteins Message-Id: <-44393-110416131027-14187-Kk3j8A9mNVWgouhxb/SUVg++server.ccl.net> X-Original-From: Rajan Chaudhari Content-Type: multipart/alternative; boundary="_a46d62f5-2e51-45b6-b4fd-911a42f696c1_" Date: Sat, 16 Apr 2011 13:10:16 -0400 MIME-Version: 1.0 Sent to CCL by: Rajan Chaudhari [rchaudhari]-[mail.usp.edu] --_a46d62f5-2e51-45b6-b4fd-911a42f696c1_ Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Hi Poonam=2C 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_manu= al/plop_manual.htm=20 Autodock: http://autodock.scripps.edu/faqs-help/faq/faqsection_view?section=3DScienti= fic%20Questions How can I set up the protonation state of my histidine sidechains?Histidine= s can be neutral or positively charged. When neutral=2C they can be protona= ted at the delta (HD1) or epsilon (HE2) positions. How can I set these up?U= sing ADT There is a command in ADT to help you decide on the protonation of the Hist= idines=2C but you have to load the commands before you can use it: go to "F= ile > Load Module" and then scroll down=2C click on "repairCommands"=2C and= then click "Load Module" followed by "Dismiss". Now=2C go to "Edit > Hydro= gens > Edit Histidine Hydrogens". If there are any histidines in your molecule=2C a panel will open up listin= g each histidine residue along with a row of radio buttons. You can use the= se to choose whether each histidine should be neutral=2C HD1=3B neutral=2C = HE2=3B or protonated. Using Reduce/Molprobity There is a very nice tool called Reduce (with a web-accessible front end ca= lled Molprobity) that can be used for adding hydrogens and optimising the h= ydrogen-bond network by flipping amido groups in Asn and Gln sidechains=2C = and His imidazole rings by 180=BA. It can also be used for evaluating the q= uality of your protein structure. See: Word=2C et al. (1999) "Asparagine and glutamine: using hydrogen atom contac= ts in the choice of sidechain amide orientation" J. Mol. Biol. 285=2C 1733-= 1745. You need to study your receptor's active site as well as mechanism of actio= n of binding ligand. you will get idea about protonation state of amino aci= ds before the ligand interaction and after ligand interaction. Hope this helps. Best Luck! Regards=2CRajan > From: owner-chemistry,ccl.net To: rchaudhari,mail.usp.edu Subject: CCL: Docking small molecules in the binding site of metalloprotein= s Date: Fri=2C 15 Apr 2011 16:08:01 -0600 Hello I am trying to dock some small molecules with a metalloprotein having manga= nese ions in its binding site.The binding site of my receptor protein comprises mostly His=2CAsp=2Cand Glu residues and it is known that the pres= ence of metal ions can alter the hydration and protonation state of these amino aci= d 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 residue= s in the binding site.I am using Surflex-Dock (Tripos Inc.) and Autodock for doc= king studies.Also=2C please suggest me some relevant articles in this regar= d. Thank you =20 Prija Ponnan=20 =20 Research Student Department of Chemistry University of Delhi Delhi-110007=2C India & Canadian Commonwealth Scholarship Program Scholar College of Pharmacy and Nutrition University of Saskatchewan Saskatoon=2CSKN5C9=2CCanada =20 = --_a46d62f5-2e51-45b6-b4fd-911a42f696c1_ Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Hi Poonam=2C

Read the following a= rticle:

=

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

PLOP is free for = academic use. =3B

Manual: http://www.jacobsonlab.org/plop_manual/plop= _manual.htm =3B

Autodock:

http://autodock.scripps.ed= u/faqs-help/faq/faqsection_view?section=3DScientific%20Questions

<= meta charset=3D"utf-8">

How can I set up the protonation state of my histidine sidechains?<= /h3>
Histidines can be neutral or positively charged. When n= eutral=2C they can be protonated at the delta (HD1) or epsilon (HE2) positi= ons. How can I set these up?
Using ADT

There is a command in ADT to help= you decide on the protonation of the Histidines=2C but you have to load th= e commands before you can use it: go to "File >=3B Load Module" and then = scroll down=2C click on "repairCommands"=2C and then click "Load Module" fo= llowed by "Dismiss". Now=2C go to "Edit >=3B Hydrogens >=3B Edit Histid= ine Hydrogens".

If there are any histidines in your molecule=2C a pa= nel will open up listing each histidine residue along with a row of radio b= uttons. You can use these to choose whether each histidine should be neutra= l=2C HD1=3B neutral=2C HE2=3B or protonated.

Using Reduce/Molprobity

There is a very nice tool called&nb= sp=3BReduce&nbs= p=3B(with a web-accessible front end called =3BMolprobity) that can be used for adding hydrogens =3B= and =3Boptimising the hydrogen-bond network by flipping amido groups in= Asn and Gln sidechains=2C and His imidazole rings by 180=BA. It can also b= e used for evaluating the quality of your protein structure. See:

Wo= rd=2C =3Bet al. =3B(1= 999) "Asparagine and glutamine: using hydrogen atom contacts in the choice = of sidechain amide orientation" = =3BJ. Mol. Biol. =3B285=2C 1733-1745.

<= div>You need to= study your receptor's active site as well as mechanism of action of bindin= g ligand. you will get idea about protonation state of amino acids before t= he ligand interaction and after ligand interaction.

Hope th= is helps. =3BBest Luck!

Regards=2C

Rajan<= /font>

From: owner-chemistry,ccl.net
<= font class=3D"Apple-style-span" face=3D"Tahoma" size=3D"2">To: rchaudhari,m= ail.usp.edu
Subject: CCL: Docking small molecules in the binding site of metallo= proteins
Date: Fri=2C 15 Apr 2011 16:08:01 -0600

Hello

I am trying to dock some s= mall molecules with a metalloprotein having manganese ions in its binding s= ite.The binding site of my receptor protein comprises mostly His=2CAsp=2Cand Glu residues and it is known that the pres= ence of metal ions can alter the hydration and protonation state of these amino aci= d 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 residue= s in the binding site.I am using Surflex-Dock (Tripos Inc.) and Autodock for docking stu= dies.Also=2C please suggest me some relevant articles in this regard.

Thank = you
&= nbsp=3B

Prija Ponnan=20

=3B

Research Student<= /div>

Department of Che= mistry

University of Del= hi

Delhi-110007=2C I= ndia

&=3B

Canadian Commonwe= alth Scholarship Program Scholar

College of Pharma= cy and Nutrition

University of Sas= katchewan

Saskatoon=2CSKN5C= 9=2CCanada

=3B

= --_a46d62f5-2e51-45b6-b4fd-911a42f696c1_--