From TOMKINSON_NP@fisonspharm.co.uk Thu Feb 9 06:39:10 1995 Received: from bit158.fisonspharm.co.uk for TOMKINSON_NP@fisonspharm.co.uk by www.ccl.net (8.6.9/930601.1506) id FAA22447; Thu, 9 Feb 1995 05:48:36 -0500 Received: from mr.fisonspharm.co.uk by BIT158.FISONSPHARM.CO.UK (PMDF V4.3-10 #6968) id <01HMUCS2YAE8000RWB@BIT158.FISONSPHARM.CO.UK>; Thu, 09 Feb 1995 10:48:44 +0000 (GMT) Received: with PMDF-MR; Thu, 9 Feb 1995 10:45:45 GMT MR-Received: by mta IOS; Relayed; Thu, 09 Feb 1995 10:46:00 +0000 MR-Received: by mta BIT158; Relayed; Thu, 09 Feb 1995 10:48:23 +0000 Alternate-recipient: prohibited Disclose-recipients: prohibited Date: Fri, 03 Feb 1995 15:39:00 +0000 (GMT) From: Nicholas Tomkinson Subject: charges schemes with CoMFA To: chemistry%ccl.net%smtp%WPC%IOS@mr.fisonspharm.co.uk Message-id: <01HMUCS698T2000RWB@mr.fisonspharm.co.uk> MIME-version: 1.0 Content-type: TEXT/PLAIN; CHARSET=US-ASCII Content-transfer-encoding: 7BIT Posting-date: Thu, 09 Feb 1995 10:42:00 +0000 (GMT) Importance: normal Priority: normal X400-MTS-identifier: [;54540190205991/327052@UKC] A1-type: MAIL Hop-count: 3 This may be a FAQ but I didn't see anything remotely connected to this subject in the archive. If looking at small molecules (doing conformational analysis, CoMFA and the like) one needs to calculate point charges, what would be the preferred method. I want to be consistent throughout the ranges of molecules I might look at and time may be an issue so that rules out ab initio methods. I have seen papers (Aleman C. et al J. Comp. Chem. vol 14 1993 799-808 Besler et al J. Comp. Chem. 1990 vol 11 431-439 for example) that suggest that MNDO ESP charges show good agreement with ab initio. I can see 2 disadvantages with this, PM3 seems to be more general than MNDO (I often use molecules with sulphur) and ESP seems dreadfully slow on my machine. So at the moment I am using PM3 Mulliken charges. The CoMFA manual suggests that models are charge-scheme insensitive but doesnt give any examples. In addition, I am using a distance-dependant dielectric but I am not convinced this is best for small molecules. Is there anyone out there with experience in CoMFA and conformational searching in small molecules in particular who either has done or has references to validation of any particular charge/non- bonded scheme for this sort of study? As usual I will summarise if there is anything forthcoming. Thanks in advance Nick Tomkinson tomkinson_np@fisonspharm.co.uk