Rational Drug Design (better late than never)

From: balbes - at - osiris.rti.org (Lisa Balbes)
Subject: Rational Drug Design (better late than never)
Date: Thu, 12 Dec 91 15:07:54 EST
 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.-