Subject: Binding Energy by MM. Summary.

From: ramon kleber da rocha <[email-masked]>
Date: Fri, 31 Oct 1997 13:55:57 -0200 (BDB)

Dear CCLers,
	About three weeks ago I posted a message about binding energy
by molecular mechanics. I would like to thank to all of you that have
replied to my help question. 
	Here is my original post:
        
	Dear CCLers,
	I would appreciate any help in getting some references (comments
will be very appreciated) on how to calculate the interaction (binding)
energy in systems like drug-receptor by using only molecular mechanics
(molecular minimization and dynamics). 
	What kind of relationship can be make about the energy calculated
by molecular mechanics (energy of forcefield)  and energy of Gibbs (delta
G), and what background theoretical is necessary to do that.
	I will sumarize.
	Best regards.
	Ramon.

	Here is the replies. Is included the address of all that replied
my question:

From: "Volkhard Helms" <[email-masked]>

you might be interested in the following study :

HELMS, V., E. DEPREZ, E. GILL, C. BARRET, G. HUI BON HOA, R.C. WADE (1996)
Biochemistry, Vol. 35, p.1485-1499. Improved binding of cytochrome P450cam
substrate
analogues designed to fill extra space in the substrate binding pocket .

From:"Fernando Danilo Gonzalez Nilo" <[email-masked]>

	Con el InsightII 950 es posible calcular la energia libre de 
enlace, con Discover_3/EnergyAnalyse, con este modulo puedes seleccionar 
dos subset y calcular la energia de interaccion.
Para mas detalles teorico busca bibliografia de Johan Aqvist, una de sus 
publicaciones respecto a este tema esta en:
Protein Engineering vol 8, no 11, pp 1137-1144, 1995, es un buen ejemplo 
de esta tecnica.

Suerte!

From: "M. Rami Reddy" <[email-masked]>

         The following papers would be helpful for calculating binding 
energies using molecular mechanics calculations.
        
        J. Med. Chem. vol 39, pages 705-712 (1996) 
        
        J. Med. Chem. vol 38, pages 305-317 (1995)
        
        J. Am. Chem. Soc. Vol 118, pages 3959-3969 (1996)

Good Luck,

From: "Dr. Mike Gilson" <[email-masked]>

The statistical-thermodynamic basis for computation of binding
affinities: A critical review.  Michael K. Gilson and James A. Given
and Bruce L. Bush and J. Andrew McCammon,
Biophys. J. 72:1047-1069,1997.

Best regards,

From: "Dr. Chris L. Waller" <[email-masked]>

Please see:

 R.D. Head, M.L. Smythe, T.I. Oprea, C.L. Waller, S.M. Greene, G.R.
Marshall, "VALIDATE: A New Method For The Receptor-Based Prediction Of
Binding Affinities Of Novel Ligands." J. Am. Chem. Soc. 1996, 118,
3959-3969 and references cited therein.

Regards,

From: "John Marelius" <[email-masked]>

you may want to take a look at the linear interaction energy (LIE) method
introduced by Aqvist et al., 1994 for calculating absolute free
energies of binding. It is a semi-empirical method which is
computationally less expensive than FEP. It is still similar to FEP in
that it is based on thermodynamic cycles and includes thermal
conformational sampling.
However, the method involves only simulations of the two physical states
(bound and free ligand) and requires no transformation processes.

The method and some applications are described in:
  Aqvist, J., Medina, C. and Samuelsson, J.E., Protein Eng., 7 (1994) 385.
  Aqvist, J. and Mowbray, S.L., J. Biol. Chem., 270 (1995) 9978.
  Aqvist, J., J. Comp. Chem., 17 (1996) 1587.
  Hulten, J., Bonham, N.M., Nillroth, U., Hansson, T., Zuccarello, G.,
Bouzide, A., Aqvist, J., Classon, B., Danielsson, H., Karlen, A.,
Kvarnstrom, I., Samuelsson, B. and Hallberg, A., J. Med. Chem., 40 (1997)
885.
  Hansson, T. and Aqvist, J., Protein Eng., 8 (1995) 1137.
  Hansson, T., Marelius, J. and Aqvist, J., J. Comput.-Aided Mol. Design,
1998, in press.

regards,
	
____________________________________________________________________________
Ramon Kleber da Rocha                                  VOICE +55-31-499-5765
e-mail [email-masked]                     FAX   +55-31-499-5700

Laboratorio de Espectroscopia e Modelagem Molecular 
Nucleo de Estudos em Quimica Medicinal - NEQUIM
Departamento de Quimica - Instituto de Ciencias Exatas
Universidade Federal de Minas Gerais
Av. Presidente Antonio Carlos, 6627 Campus Pampulha
CEP 31-270-901 - Belo Horizonte - Minas Gerais - Brasil
____________________________________________________________________________