Subject: Binding energy by MM

From: ramon kleber da rocha <[email-masked]>
Date: Fri, 10 Oct 1997 18:45:29 -0200 (BDB)

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.

____________________________________________________________________________
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
____________________________________________________________________________

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From: "Volkhard Helms" <[email-masked]>
Date: Fri, 10 Oct 1997 15:04:55 -0700

Hi Ramon,

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 .

This paper stresses the importance of properly accounting for all solvent
contributions.
Binding energies to cytochrome P450cam were calculated from molecular dynamics
simulations for a series of camphor derivatives, and agreed very well with
experimental
binding enthalpies.
Yet, the experimental binding free energies follow a completely different trend
 ...

Hope this example gives you some ideas.

Volkhard Helms
Dept. of Chemistry and Biochemistry
UCSD San Diego