Subject: Re: CCL:Re: CCL:FEP binding energy

From: Rami Reddy <[email-masked]>
Date: Wed, 9 Jul 1997 05:19:46 +48000

On 7 Jul 1997, Arne Elofsson wrote:

> Soaring Bear <[email-masked]> writes:
> 
> > Greetings:
> > 
> > 
> > I have noticed that published studies of FEP energy calculations
> > of inhibitor binding are largely on a pairwise basis, comparing
> > small numbers of inhibitors (presumably due to computational cost).
> > I am interested in locating studies which have compared at least
> > a dozen.   I would appreciate any references.      Also, any
> > examples with structure based affinity calculation (especially
> > linear response approximation)?
> > 
>
Dear Dr. Bear,

Reddy et al evaluated a large set of related analogs using 
computer-assisted drug design methods that combine molecular mechanics, 
dynamics, FEP calculations, inhibitor design, synthesis, biochemical 
testing, and crystallographic structure determination of the 
protein-inhibitor complexes.  The calculated relative binding free 
energies were successfully incorporated into the design of novel HIV1 
protese inhibitors.  This study involved a large set of molecules whose 
relative binding affinities were predicted using FEP method prior to 
synthesis, and were later confirmed by experimental measurements. 

Reddy et al. J. Med. Chem. 37 (1994), 1145-1152 

If you have any questions or comments please let know.

M. Rami Reddy
Metabasis Therapeutics, Inc
Email: [email-masked]