Subject: Re: CCL:FlexX Docking

From: szilva!at!computer.org
Date: Mon, 22 Dec 2003 08:29:22 +0100 (CET)

On Sun, 21 Dec 2003, Sivanesan Dakshanamurthy wrote:

> Could anybody explain the reason, why docking may not be able to
> reproduce the native ligand in the thier structure.

Hello, scoring fucntions are experimental (heuristic) functions -
therefore they are only approximations. You need approximations since you
want to dock libraries with numerous ligands. Somebody asked recently why
do we need different scoring funcions: simply because they are different
sort of approximations. If you can get the native ligand as a first from a
random library then you are very lucky. Usually native ligands are in the
top 1% or 5% (or ranked even worse) but rarely are the very first. You
need special pre- and post-filtering procedures to get a reasonable hit
library with docking.

Unfortunatelly the CLL arhive search is not working, I sent these
references already:

M. Stahl & M. Rarey:
Detailed Analysis of Scoring Functions for Virtual Screening
J. Med. Chem. 2001, 44, 1035-1042

C. Bissantz, G. Folkers, and D. Rognan:
Protein-Based Virtual Screening of Chemical Databases. 1. Evaluation of
Different Docking/Scoring Combinations
J. Med. Chem. 2000, 43, 4759-4767

Also the Glide tech note is very useful:
http://www.schrodinger.com/docs/fd2_2002_2/pdf/fd25_technical_notes.pdf
(it is analysing only one docking platform but with many targets, check
the "Database enrichment" section).

Cheers:
Szilva