From owner-chemistry@ccl.net Wed Jun 4 04:43:01 2008 From: "Jens Thomas j.m.h.thomas:_:dl.ac.uk" To: CCL Subject: CCL:G: Morphy98 Message-Id: <-37089-080604043816-19052-bvUGZXQ54wNX6W7bCBH09w:server.ccl.net> X-Original-From: Jens Thomas Content-Transfer-Encoding: 7bit Content-Type: text/plain; charset=ISO-8859-1; format=flowed Date: Wed, 04 Jun 2008 09:37:17 +0100 MIME-Version: 1.0 Sent to CCL by: Jens Thomas [j.m.h.thomas=-=dl.ac.uk] Hi Alex, I don't have access to Morphy98, but if you can work out what the problem is with the way that GAMESS-UK outputs its .wfn file, I'll patch the code to make sure that the output is compatible in the future. Best wishes, Jens Alex Naden anaden{}fsmail.net wrote: > Sent to CCL by: "Alex Naden" [anaden]_[fsmail.net] > Hi Mike, > > Thank you for the information. It feels better somehow knowing that someone else did something similar! > > I will try and look at the possible differences in the .wfn files again, in case if there is something that I have not noticed before (I have some Gaussian .wfn files). > > Regards, > > Alex> > > > > -- =================================================================== Jens Thomas, email: j.m.h.thomas_-_dl.ac.uk STFC Daresbury Lab, tel: +44-1925-603849 Warrington, fax: +44-1925-603634 WA4 4AD, UK. http: http://www.cse.scitech.ac.uk =================================================================== From owner-chemistry@ccl.net Wed Jun 4 12:22:00 2008 From: "James Prudhomme jprudhomme::healthtech.com" To: CCL Subject: CCL: Structure-Based Drug Design Conference this Month in Boston Message-Id: <-37090-080604120527-3665-McAE+cC9uK+BECo5KzrWHQ() server.ccl.net> X-Original-From: "James Prudhomme" Date: Wed, 4 Jun 2008 12:05:23 -0400 Sent to CCL by: "James Prudhomme" [jprudhomme * healthtech.com] Hi, Please see below for the agenda for CHIs Structure-Based Drug Design conference being held on June 25-27, 2008 at the World Trade Center in Boston, MA. If you are interested and want to attend, sign-up at www.healthtech.com/sbd/overview.aspx Wednesday, June 25 PRE-CONFERENCE WORKSHOP Designing Kinase Inhibitors Presenters: - Stefan Knapp, Ph.D., Principal Investigator, Phosphorylation Dependent Signalling Group, Structural Genomics Consortium, Oxford University, UK - Roman Hillig, Ph.D., Scientist, Structural Biology/Lead Discovery, Bayer Schering Pharma AG - Glenn Noronha, Ph.D., Director of Chemistry, TargeGen, Inc. - Jeffrey Liao, Ph.D., TransTech Pharma, Inc. - Gregg Siegal, Ph.D., CSO, ZoBio, The Netherlands Thursday, June 26 - Main Conference COMPUTATIONAL-BASED PROTEIN DESIGN Recent Progress in Computational Protein Design: Designing Combinatorial Protein Libraries Stephen Mayo, Ph.D., Professor of Biology and Chemistry, California Institute of Technology Structure Based Design of Inhibitors of Imatinib-resistant Mutants of Bcr-Abl Kinase David Dalgarno, Ph.D., Vice President, Research Technologies, ARIAD Pharmaceuticals Inc. CHALLENGES OF DOCKING AND SCREENING: SPEED, COST, AND QUALITY OF RESULTS Virtual Screening Enrichment Studies: The Devil Is in the Details Andrew Good, Ph.D., Principal Scientist, Computer Assisted Drug Design, Bristol-Myers Squibb Technology Spotlight: eHiTS Lightning Redefines the State-of-the-art for Structure-Based Virtual Screening Zsolt Zsoldos, Co-Founder and CSO, SimBioSys Co-presentation: The Fine Details Matter! Learnings & Challenges from De Novo Design & Docking Jonathan S. Mason, Ph.D., Chief Scientist & Divisional Director, Computational Chemistry & Structural Biology, Lundbeck Research (Denmark);Lena Tagmose, Ph.D., Head of Section, Computational Chemistry, Lundbeck Research (Denmark) In silico Discovery and NMR Validation of Transcriptional Inhibitors: Targeting a Requisite Interface Alan C. Rigby Ph.D., Assistant Professor of Medicine, Harvard Medical School High Resolution Modeling of Protein-Ligand Interactions Richard A. Friesner, Ph.D., Professor of Chemistry, Columbia University On the Applicability of GPCR in-silico Models to Drug Discovery: A Comparison between Crystal Structure and Molecular Models of the Beta2-Adrenergic Receptor in Complex with Carazolol Stefano Costanzi, Ph.D., Head of the Molecular Modeling Unit, Laboratory of Biological Modeling, NIH, NIDDK Hosted Luncheon Workshop: Recent Advances in the Treatment of Receptor Flexibility for Accurate Docking and Scoring B. Woody Sherman, Ph.D., Director, Applications Science, Schrodinger, Inc. HIT AND LEAD OPTIMIZATION The Significance of Unconventional Hydrogen Bonds in Structure Based Drug Design Gergely Toth, Ph.D., Scientist, Computational Chemistry and Biology, Elan Pharmaceuticals Free Energy Computations in Drug Discovery and Optimization Matthew Clark, Ph.D., Senior Director of Scientific Computation, Locus Pharmaceuticals Technology Spotlight: Structure-based Discovery of SIRT1 Activators Utilizing Fragments from HTS Hits Anthony J. Trippe, Sr. Innovation Manager, New Product Development, Chemical Abstracts Service (CAS) Structure Based Design of BCR-Abl Kinase Inhibitors with Activity against the T315I Mutant Andreas Gosberg, Ph.D., Senior Scientist II, Medicinal Chemistry, SGX Pharmaceuticals Structural-Informed Discovery of CDK2 Inhibitors Jos S. Duca, Ph.D., Principal Scientist, Department of Drug Design, Schering-Plough Research Institute PROTEIN-PROTEIN INTERACTIONS: THERAPEUTIC TARGETS AND DRUG DISCOVERY Targeting Protein-Protein Complexes from the Viral Replication Machinery through a Multidisciplinary Platform Xavier J. Morelli, Ph.D., Principal Investigator, NMR and Drug Design, National Center for Scientific Research (CNRS) Stapled Helical Peptides: Novel Synthetic Biologics Tomi Sawyer, Ph.D., Chief Scientific Officer, AILERON Therapeutics Friday, June 27 - Main Conference EXPERIMENTAL APPROACHES Bridging the Affinity Gap: Application of Label-free Methods in Fragment-based Lead Generation Stefan Geschwindner, Ph.D., Principal Scientist and Team Leader, Protein Engineering, Global Structural Chemistry, AstraZeneca R&D Mlndal Protonate 3D: Assignment of Protonation State and Geometry in Macromolecular Structures Paul Labute, Ph.D., President, Chemical Computing Group Inc. Use of Mass Spectrometry to Help Drive the Design of a Drug Candidate from Inception to Development Jennifer Nemeth, Ph.D., Principal Research Scientist, Protein Engineering, Centocor Research and Development Technology Spotlight: Exploring Receptor-Flexible Docking C.M. (Venkat) Venkatachalam, Ph.D., Fellow, Accelrys, Inc. STRUCTURE-BASED MODELING OF GPCRs 5HT1A and 5HT6 Ligating Drugs from Computer Model to Clinical Trial Sharon Shacham, Ph.D., Vice President, Drug Development, EPIX Pharmaceuticals CASE STUDIES The Design and Synthesis of Novel Second Generation HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Thomas J. Tucker, Ph.D., Senior Research Fellow, Dept. of Medicinal Chemistry, Merck Research Laboratories Structure Based Drug Design of HIV-1 Reverse Transcriptase Inhibitors Christopher Phillips, Ph.D., Senior Principal Scientist, Exploratory Medicinal Sciences, Pfizer Global Research and Development Technology Spotlight: Identification of Pyk2 FERM Ligands by Combining Protein Similarity Assessment, Pharmacophore Prediction, and In Silico Screening Lei Wang, Ph.D., Manager, Application Science, Tripos International > From Virtual Screening to Clinic: Discovery of Cevoglitazar T. R. Vedananda, Ph.D., Program Head, Diabetes & Metabolism, Novartis The Discovery of OSI-906: A Novel, Potent, Orally Bioavailable Imidazopyrazine-derived Insulin-like Growth Factor-I Receptor (IGF-1R) Inhibitor with Antitumor Activity Mark Mulvihill, Ph.D., Associate Director of Chemistry, Oncology, OSI Pharmaceuticals Structure-based Discovery of Clinical Candidates for Hsp90 Roderick E. Hubbard, Senior Fellow, Vernalis and Professor, University of York Please let me know if you have any questions. All the speaker abstracts are available at the website I referenced above. Regards, Jim Prudhomme Cambridge Healthtech Institute 250 First Avenue, Suite 300 Needham, MA 02494 Direct: 781-972-5486 Fax: 781-972-5425 www.healthtech.com From owner-chemistry@ccl.net Wed Jun 4 14:00:01 2008 From: "Alex Naden anaden{}fsmail.net" To: CCL Subject: CCL: Morphy98 Message-Id: <-37091-080604135817-12926-1SMmjSR6vkaPLadYLEu52Q*o*server.ccl.net> X-Original-From: "Alex Naden" Date: Wed, 4 Jun 2008 13:58:13 -0400 Sent to CCL by: "Alex Naden" [anaden^^fsmail.net] Hi Jens, Thank you for the letter. I will try and use Mike's advice to find out if there are any inconsistencies between the .wfn files and also to check for my own errors in the process. It might take some time however, as I need to work out how to write the script for reformatting as well. I also think that I might need to clarify some legal aspects with a certain party involved, but I will get back to you as soon as there is any information. Best wishes, Alex ========================================================================== Hi Alex, I don't have access to Morphy98, but if you can work out what the problem is with the way that GAMESS-UK outputs its .wfn file, I'll patch the code to make sure that the output is compatible in the future. Best wishes, Jens From owner-chemistry@ccl.net Wed Jun 4 14:35:00 2008 From: "Michael Xu michael.drug.design ~~ gmail.com" To: CCL Subject: CCL: agonist-antagonist-inhibitor Message-Id: <-37092-080604122539-8172-jGbjy0dc6nQ7fnf+gCRD1A#%#server.ccl.net> X-Original-From: "Michael Xu" Content-Type: multipart/alternative; boundary="----=_Part_4367_19146543.1212593353477" Date: Wed, 4 Jun 2008 11:29:12 -0400 MIME-Version: 1.0 Sent to CCL by: "Michael Xu" [michael.drug.design#,#gmail.com] ------=_Part_4367_19146543.1212593353477 Content-Type: text/plain; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline Hi, all Recent days, some experts gave a wonderful explanation of IC50, Ki, Kd, and deltaG. I am confused about some words several years. Can anyone give some discussion? Inhibitor Agonist Antagonist Inverse agonist. Is the inhibitor used for Enzyme-substrate-inhibitor? And the agonist/antagonist used for protein-ligand? Thanks in advance. Mike. ------=_Part_4367_19146543.1212593353477 Content-Type: text/html; charset=ISO-8859-1 Content-Transfer-Encoding: 7bit Content-Disposition: inline

Hi, all

 

Recent days, some experts gave a wonderful explanation of IC50, Ki, Kd, and deltaG.

 

I am confused about some words several years. Can anyone give some discussion?

 

Inhibitor

Agonist

Antagonist

Inverse agonist.

 

Is the inhibitor used for Enzyme-substrate-inhibitor?

And the agonist/antagonist used for protein-ligand?

 

Thanks in advance.

 

Mike.

------=_Part_4367_19146543.1212593353477-- From owner-chemistry@ccl.net Wed Jun 4 16:59:00 2008 From: "Jeff Hammond jeff.science++gmail.com" To: CCL Subject: CCL: computer for high-level QC calculations Message-Id: <-37093-080604152855-11623-SFYChSIiUjPQW0OF3FaRXA:server.ccl.net> X-Original-From: "Jeff Hammond" Date: Wed, 4 Jun 2008 15:28:51 -0400 Sent to CCL by: "Jeff Hammond" [jeff.science-*-gmail.com] Pablo, An SGI Altix 4700 is a great machine to run NWChem on, as the code runs extremely well on Itanium processors and will utilize every last drop of shared memory if you ask it to. GAMESS, PQS and Aces II (MAB) utilize disk for large CC calculations and were designed to run on machines with more modest interconnects. That is not to say that they won't benefit from a higher network bandwidth and lower latency, but I don't think you'll get your money's worth. For these codes, you're probably better off buying a machine like the ones the developers demonstrate those codes on, which is a Beowulf cluster with striped SCSI disk arrays and channel-bonded Ethernet (approximately). Aces 3 is quite new, but should run well on an SGI Altix, assuming it is supported. The Aces 3 design paradigm permits platform-specific optimization which might be able to exploit the special features of the Altix. You can refer to the following articles which discuss the relative performance of various codes in parallel. Each paper notes the hardware that the code was tested and timed on. Aces II (MAB) - J. Chem. Theory Comput., 4 (1), 64 -74, 2008 - http://pubs.acs.org/cgi-bin/abstract.cgi/jctcce/2008/4/i01/abs/ct700152c.html GAMESS - J. Chem. Theory Comput., 3 (4), 1312 -1328, 2007 - http://pubs.acs.org/cgi-bin/abstract.cgi/jctcce/2007/3/i04/abs/ct600366k.html PQS - J. Chem. Theory Comput., 3 (4), 1368 -1377, 2007 - http://pubs.acs.org/cgi-bin/abstract.cgi/jctcce/2007/3/i04/abs/ct700048u.html Aces 3 (QTP) J. Chem. Phys. 128, 194104 (2008) - http://link.aip.org/link/?JCPSA6/128/194104/1 NWChem (old CC code) J. Phys. Chem. A, 109 (31), 6934 -6938, 2005 - http://pubs.acs.org/cgi-bin/abstract.cgi/jpcafh/2005/109/i31/abs/jp044564r.html NWChem (TCE) J. Chem. Phys. 127, 144105 (2007) - http://link.aip.org/link/?JCP/127/144105 (The timing data in this paper is already obsolete, but the scalability is representative.) I am not aware of any reason why Itanium would be an issue. The Intel compilers do a fine job of generating fast code and this chip is the best available for DGEMM, which is the fundamental kernel for coupled-cluster codes. Best, Jeff From owner-chemistry@ccl.net Wed Jun 4 17:33:00 2008 From: "Karen.Green::sanofi-aventis.com" To: CCL Subject: CCL: agonist-antagonist-inhibitor Message-Id: <-37094-080604160442-1342-lqcYtQU6pCDssK4bWuJCYQ#server.ccl.net> X-Original-From: Content-class: urn:content-classes:message Content-Type: multipart/alternative; boundary="----_=_NextPart_001_01C8C679.A5FAD0A5" Date: Wed, 4 Jun 2008 12:31:55 -0700 MIME-Version: 1.0 Sent to CCL by: [Karen.Green(a)sanofi-aventis.com] This is a multi-part message in MIME format. ------_=_NextPart_001_01C8C679.A5FAD0A5 Content-Type: text/plain; charset="us-ascii" Content-Transfer-Encoding: quoted-printable I would recommend the monograph: Eds. Seifert, R.; Wieland. "G Protein-Coupled Receptors as Drug Targes: Analysis of Activation and Constitutive Activity"; Methods and Principles in Medicinal Chemistry 24; Wiley-VCH c. 2005. =20 ________________________________ > From: owner-chemistry^ccl.net [mailto:owner-chemistry^ccl.net]=20 Sent: Wednesday, June 04, 2008 8:29 AM To: Green, Karen R&D/US Subject: CCL: agonist-antagonist-inhibitor Hi, all =20 Recent days, some experts gave a wonderful explanation of IC50, Ki, Kd, and deltaG. =20 I am confused about some words several years. Can anyone give some discussion? =20 Inhibitor Agonist Antagonist Inverse agonist.=20 =20 Is the inhibitor used for Enzyme-substrate-inhibitor? And the agonist/antagonist used for protein-ligand? =20 Thanks in advance. =20 Mike.=20 ------_=_NextPart_001_01C8C679.A5FAD0A5 Content-Type: text/html; charset="us-ascii" Content-Transfer-Encoding: quoted-printable
I would=20 recommend the monograph:
Eds.=20 Seifert, R.; Wieland. "G=20 Protein-Coupled Receptors as Drug Targes:  Analysis of Activation = and=20 Constitutive Activity"; Methods and Principles in Medicinal Chemistry = 24;=20 Wiley-VCH   c. 2005.
 
From: owner-chemistry^ccl.net=20 [mailto:owner-chemistry^ccl.net]
Sent: Wednesday, June 04, = 2008 8:29=20 AM
To: Green, Karen R&D/US
Subject: CCL:=20 agonist-antagonist-inhibitor

Hi, all

 

Recent days, = some experts=20 gave a wonderful explanation of IC50, Ki, Kd, and=20 deltaG.

 

I am = confused about some=20 words several years. Can anyone give some = discussion?

 

Inhibitor

Agonist

Antagonist

Inverse = agonist.=20

 

Is the = inhibitor used for=20 Enzyme-substrate-inhibitor?

And the = agonist/antagonist=20 used for protein-ligand?

 

Thanks in=20 advance.

 

Mike.=20

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