From chemistry-request;at;ccl.net Thu Dec 12 15:32:48 1991
Date: Thu, 12 Dec 91 15:07:54 EST
From: balbes ^at^ osiris.rti.org (Lisa Balbes)
To: chemistry- at -ccl.net, sybyl- at -quant.chem.rpi.edu
Subject: Rational Drug Design (better late than never)
Status: R


As promised, I have compiled a summary of references and information
I gathered in reading all the responses to my (much) earlier request.
All typos and mistakes are mine.

A brief index/outline follows - for the entire 282 line file,
email me at balbes ":at:" osiris.rti.org

____________________________
Introduction:

Steps in rational drug design -

1.  Determine receptor site of interest.
2.  Build model of active site (receptor).
        a.  Model entire protein - from xray of protein, homology modeling
      or
        b.  build pharmacophore (geometric description of the minimal
                requirements of shape and charge complimentarity)
3.  Develop inhibitor structures that fit active site model and dock.
4.  Quantitate interaction, to predict activity of new compounds.
5.  Synthesize compounds; evaluate their activity in the system of interest.
6.  Refine (2), repeat (3) - (5).
7.  Find effective, safe, synthesizable compound.  Patent.  Sell. $$$$$$$.
        Either a) start again at (1) or b) retire to Hawaii.


********** step 2 *******************************
GRID method of Peter J. Goodford
********** step 3 *******************************
Distance Geometry Devloped by Crippen and co-workers
********** step 3 (docking) **********************
DOCK Irwin D. Kuntz, Jr.
********** steps 3, 4 ******************************
GROW method of Moon and Howe (proprietary program, but methods useful).
************* step 4 *************************
Free Energy Perturbation
************* step 4 *************************
Min/MD cycling

                GENERAL APPROACHES
^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
Quantitative Structure Activity Relationship (QSAR)
Active Analog Approach
Simulated Annealing
Molecular Dynamics (MD)

^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^
		General Reviews


%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%% standard disclaimer %%%%
 Lisa M. Balbes, Ph.D.     		       phone: 919-541-6563
 Research Triangle Institute, PO Box 12194     vmail: 919-541-6767, xt 6563    
 Research Triangle Park,  NC 27709-2194        email: balbes {*at*} osiris.rti.org 
  					     
- This came directly from a computer and should not be doubted or disbelieved.-