From owner-chemistry@ccl.net Thu Oct 15 02:46:00 2020 From: "HOUSTON Douglas DouglasR.Houston[#]ed.ac.uk" To: CCL Subject: CCL: Pharmacophore flexible search tool Message-Id: <-54183-201015024450-9343-2NbaQmdzjXHCm+8GjNpz2w(!)server.ccl.net> X-Original-From: HOUSTON Douglas Content-Language: en-GB Content-Type: multipart/alternative; boundary="_000_DBAPR05MB7047463D3C491ED2D8D9E177A8020DBAPR05MB7047eurp_" Date: Thu, 15 Oct 2020 06:44:37 +0000 MIME-Version: 1.0 Sent to CCL by: HOUSTON Douglas [DouglasR.Houston_+_ed.ac.uk] --_000_DBAPR05MB7047463D3C491ED2D8D9E177A8020DBAPR05MB7047eurp_ Content-Type: text/plain; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Hi Sergio, Thanks for your reply. Do you know the details of how ZINCPharmer compares = the molecules in the database with the pharmacophore? I note this from the = site: "The ZincPharmer search technology uses the Pharmer open source pharmacophore search technology to efficient= ly search a large database of fixed conformers for pharmacophore matches" There's a difference between creating a conformer library, and actually tre= ating each molecule as flexible. I already have ways of creating conformer libraries, but what results is a = coarse sampling of all possible conformations. What I'm looking for is a wa= y of treating the library compounds as actually flexible, in the same way t= hat e.g. Vina or Autodock treats the small molecule to be docked into a rec= eptor as flexible. Regards, Doug ________________________________ > From: owner-chemistry+douglasr.houston=3D=3Ded.ac.uk(-)ccl.net on behalf of Sergio Vechi vechis= m/agmail.com Sent: 19 May 2020 21:59 To: HOUSTON Douglas Subject: CCL: Pharmacophore flexible search tool Dear Doug, You can build the pharmacophore model with PharmaGist (https://bioinfo3d.cs= .tau.ac.il/PharmaGist/php.php) and search Zinc database using ZINCPharmer (= http://zincpharmer.csb.pitt.edu/). Cheers, Sergio +--------------------------------------------------------------------------= --------------------------------------+ Dr. S=E9rgio Vechi | vechism:gmail.com Associate Professor Federal University of Alagoas | Campus Arapiraca | NCEx Av. Manuel Severino Barbosa, s/n, Bom Sucesso 57309-005 Arapiraca (AL) - Brazil +--------------------------------------------------------------------------= --------------------------------------+ On Tue, May 19, 2020 at 4:35 PM HOUSTON Douglas DouglasR.Houston]![ed.ac.uk= > wrote: Hi all, Does anyone know of a free (for academics at least) chemical search tool, t= hat will screen a large compound library (say an SDF of 100,000 molecules) = against a reference pharmacophore/ligand, and treat the library compounds a= s flexible and not rigid? I've asked this before but for some reason the formatting was so screwed up= I don't think most people could read it! Regards, Doug ---------------------------------------------------------------------------= --------------- Dr. Douglas R. Houston Senior Lecturer in Computational Biochemistry Institute of Quantitative Biology, Biochemistry and Biotechnology Room 2.12, Waddington 1 Building King's Buildings University of Edinburgh Edinburgh, EH9 3BF, UK Tel. 07986875743 The University of Edinburgh is a charitable body, registered in Scotland, w= ith registration number SC005336. --_000_DBAPR05MB7047463D3C491ED2D8D9E177A8020DBAPR05MB7047eurp_ Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable
Hi Sergio,

Thanks for your reply. Do you know the details of how ZINCPharmer compares = the molecules in the database with the pharmacophore? I note this from the = site:

"The Zi= ncPharmer search technology uses the Pharme= r&= nbsp;open source pharmacophore search technology to efficiently search a large datab= ase of fixed conformers for pharmacophore matches"

There's a difference between creating a conformer library, an= d actually treating each molecule as flexible.

I already have ways of creating conformer libraries, but what= results is a coarse sampling of all possible conformations. What I'm looking for is a way of treating the libr= ary compounds as actually flexible, in the same way that e.g. Vina or Autodock treats= the small molecule to be docked into a receptor as flexible.

Regards,
Doug


From: owner-chemistry+dougl= asr.houston=3D=3Ded.ac.uk(-)ccl.net <owner-chemistry+douglasr.houston=3D= =3Ded.ac.uk(-)ccl.net> on behalf of Sergio Vechi vechism/agmail.com <owner-chemistry(-)ccl.net>
Sent: 19 May 2020 21:59
To: HOUSTON Douglas <DouglasR.Houston(-)ed.ac.uk>
Subject: CCL: Pharmacophore flexible search tool
 
= Dear Doug,
=
= You can build the pharmacophore model with PharmaGist (https://bioinfo3d.cs.tau.ac.il/Ph= armaGist/php.php) and search Zinc database using ZINCPharmer (h= ttp://zincpharmer.csb.pitt.edu/).
=
= Cheers,
=
= Sergio
+------------------------------------= ---------------------------------------------------------------------------= -+
   Dr. S=E9rgio Vechi | vechism:gmail.com           =                     &nbs= p;  
     Associate Professor
     Federal University of Alagoas | Campus Arapiraca |= NCEx
     Av. Manuel Severi= no Barbosa, s/n, Bom Sucesso
     57309-005 Ar= apiraca (AL) - Brazil               = ;         
+--------------------------------------------------------------------------= --------------------------------------+


On Tue, May 19, 2020 at 4:35 PM HOU= STON Douglas DouglasR.Houston]![ed.ac.uk &l= t;owner-chemistry|,|ccl.net> wrote:
Hi all,

Does anyone know of a free (for academics at least) chemical se= arch tool, that will screen a large compound library (say an SDF of 100,000 molecules) against a reference pharmacophor= e/ligand, and treat the library compounds as flexible and not rigid?=

I've asked this before but for some reason the formatting was so scr= ewed up I don't think most people could read it!

Regards,
Doug

--------------------------------------------------------------------= ----------------------
Dr. Douglas R. Houston
Senior Lecturer in Computational Biochemistry
Institute of Quantitative Biology, Biochemistry and Biotechnology
Room 2.12, Waddington 1 <= /span>Building
King's Buildings
University of Edinburgh
Edinburgh, EH9 3BF, UK
Tel. 07986875743

The University of Edinburgh is a charitable body, registered in Scotland, w= ith registration number SC005336.
--_000_DBAPR05MB7047463D3C491ED2D8D9E177A8020DBAPR05MB7047eurp_-- From owner-chemistry@ccl.net Thu Oct 15 17:54:01 2020 From: "Sruthi S sruthisnambiar0412!A!gmail.com" To: CCL Subject: CCL: Difference in Crystal structure and geometry optimized structure Message-Id: <-54184-201015175333-22856-aeJGnynHChmjKq1k4qyZvw{}server.ccl.net> X-Original-From: "Sruthi S" Date: Thu, 15 Oct 2020 17:53:32 -0400 Sent to CCL by: "Sruthi S" [sruthisnambiar0412!=!gmail.com] I have crystal structure of a ligand with 2 rings - one of which is an indole. On optimizing this ligand at HF/6-31F* level with a few other side chains (which were not present in the crystal structure), I get an output where the indole ring has changed its orientation by 180 degree compared to the crystal structure. Is it possible to see such a change due to the side chain? The side chains are a pyrrole rings at the end of an ethyl chain and it is right next to the indole ring. From owner-chemistry@ccl.net Thu Oct 15 19:44:01 2020 From: "David Shobe shobedavid||gmail.com" To: CCL Subject: CCL: Difference in Crystal structure and geometry optimized structure Message-Id: <-54185-201015194317-25023-Ly2wGsETIRVEQ65vxdGksw .. server.ccl.net> X-Original-From: David Shobe Content-Type: multipart/alternative; boundary="000000000000073d5405b1be363f" Date: Thu, 15 Oct 2020 18:43:00 -0500 MIME-Version: 1.0 Sent to CCL by: David Shobe [shobedavid**gmail.com] --000000000000073d5405b1be363f Content-Type: text/plain; charset="UTF-8" Is the computational geometry for an isolated molecule (i.e. gas phase)? If so, it may be crystal packing forces that cause the change in orientation. Does the geometry change when you use a different level of theory? Can you find the geometry of the exact molecule (no side chain), and is it like the crystal structure? On Thu, Oct 15, 2020, 6:28 PM Sruthi S sruthisnambiar0412!A!gmail.com < owner-chemistry::ccl.net> wrote: > > Sent to CCL by: "Sruthi S" [sruthisnambiar0412!=!gmail.com] > I have crystal structure of a ligand with 2 rings - one of which is an > indole. On optimizing this ligand at HF/6-31F* level with a few other side > chains (which were not present in the crystal structure), I get an output > where the indole ring has changed its orientation by 180 degree compared > to > the crystal structure. Is it possible to see such a change due to the side > chain? The side chains are a pyrrole rings at the end of an ethyl chain > and > it is right next to the indole ring.> > > --000000000000073d5405b1be363f Content-Type: text/html; charset="UTF-8" Content-Transfer-Encoding: quoted-printable
Is the computational geometry for an isolated molecule (i= .e. gas phase)? If so, it may be crystal packing forces that cause the chan= ge in orientation. Does the geometry change when you use a different level = of theory? Can you find the geometry of the exact molecule (no side chain),= and is it like the crystal structure?

On Thu, O= ct 15, 2020, 6:28 PM Sruthi S sruthisnambiar0412!A!gmail.com <owner-che= mistry::ccl.net> wrote:

Sent to CCL by: "Sruthi=C2=A0 S" [sruthisnambiar0412!=3D!gmail= .com]
I have crystal structure of a ligand with 2 rings - one of which is an
indole. On optimizing this ligand at HF/6-31F* level with a few other side =
chains (which were not present in the crystal structure), I get an output <= br> where the indole ring has changed its orientation by 180 degree compared to=
the crystal structure. Is it possible to see such a change due to the side =
chain? The side chains are a pyrrole rings at the end of an ethyl chain and=
it is right next to the indole ring.



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