Subject: Enhancing CoMFA: free program release

From: Arthur Wang <[email-masked]>
Date: Thu, 19 Nov 1998 20:51:12 -0800 (PST)

Dear CCLers,

Comparative Molecular Field Analysis (CoMFA) has been widely used as a
powerful 3D-QSAR tool in the field of medicinal chemistry since its birth
in the late 1980s. It usually uses a grid to map the molecular field
around the molecular aggregate and find out the relationship between the
data on the grid and bioassay activities by PLS technique. However,
several groups have reported that the orientation of the molecular
aggregate has significant influence on the final result given by such a
CoMFA procedure.  Sometimes the q2 value in cross-validation may vary as
much as 0.4 units among different orientations. 

We recently reported two enhanced sampling procedures, all-orientation
search (AOS) and all-placement search (APS), for CoMFA analysis. According
to AOS/APS, the molecular aggregate is rotated or translated
systematically within the grid and a CoMFA is performed for each
orientation or placement thus obtained. Among all the possible
orientations or placements, the one yielding the highest q2 value is
picked out. By such an exhaustive searching, the arbitrariness in the
conventional CoMFA can be eliminated and the CoMFA result is therefore
optimized. For more details about the method, please have a look at: 

Renxiao Wang, Ying Gao, Liang Liu, and Luhua Lai
"All-Orientation Search and All-Placement Search in Comparative Molecular
Field Analysis", Journal of Molecular Modeling, 4, 276-283. 

The program for performing AOS and APS is written in SYBYL/SPL script. A
SYBYL user will find it very easy to run AOS and APS. 

The program is now available to the public. You can get it via anonymous
FTP to ftp.ipc.pku.edu.cn (162.105.177.12) /pub/software/aos_aps/. 

Please forward this mail to whom may be concerned.

Best wishes,

Arthur

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_/   Renxiao Wang                     Doctoral Candidate      _/
_/   Molecular Design Laboratory                              _/
_/   Institute of Physical Chemistry, Peking University       _/
_/   Beijing 100871, P.R.China                                _/
_/                                                            _/ 
_/   E-mail: [email-masked]                            _/
_/   Tel: 86-10-62751490    Fax: 86-10-62751725               _/
_/   WWW: http://www.ipc.pku.edu.cn/~arthur/arthur.html       _/
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