Conformer program

Conformational analysis can be carried out by MO calculations by comparing the total energies of different conformations. Program packages which automatically (and analytically) compute the derivatives of the total energy, and minimize it, are by now available. 

Many approaches and methods for the generation of multiple conformations have been developed and published since the early 1980s. Below we describe briefly some of the basic concepts and methods of automatic conformer generation. However, interested readers are referred to Chapter 11, Section 7.2 in the Handbook, where the approaches to automatic generation of ensembles of conformations and the program systems that have been developed are described in detail. 

The Empirical Conformational Energy Program for Peptides, ECEPP [63, 64], is one of the first empirical interatomic potentials whose derivation is based both on gas-phase and X-ray crystal data [65], It was developed in 1975 and updated in 1983 and 1992. The actual distribution (dated May, 2000) can be downloaded without charge for academic use. 

D.R. Ripoll, H.A. Scheraga, ECEPP Empirical Conformational Energy Program for Peptides, in The Encyclopedia of Computational Chemistry, Vol. 2,... 

A range of physicochemical properties such as partial atomic charges [9] or measures of the polarizabihty [10] can be calculated, for example with the program package PETRA [11]. The topological autocorrelation vector is invariant with respect to translation, rotation, and the conformer of the molecule considered. An alignment of molecules is not necessary for the calculation of their autocorrelation vectors. 

These programs generate one low-energy conformation for each molecule. 

An overview of docking programs is given in Tabic 10.4-3. Depending on the way the conformational flexibility of the ligand is treated, docking can be either rigid or flexible. 

The input to a minimisation program consists of a set of initial coordinates for the system. The initial coordinates may come from a variety of sources. They may be obtained from an experimental technique, such as X-ray crystallography or NMR. In other cases a theoretical method is employed, such as a conformational search algorithm. A combination of experimenfal and theoretical approaches may also be used. For example, to study the behaviour of a protein in water one may take an X-ray structure of the protein and immerse it in a solvent bath, where the coordinates of the solvent molecules have been obtained from a Monte Carlo or molecular dynamics simulation. 

GeUiaar D K, G M Verkhivker, P A Rejto, C J Sherman, D B Fogel, L J Fogel and S T Freer 1995 Molecular Recognition of the Inhibitor AG-1343 by HFV-l Protease Conformationally FlexibL Docking by Evolutionary Programming. Chemistry and Biology 2 317-324. 

Empirical conformational energy program for peptides (ECEPP) is the name of both a computer program and the force field implemented in that program. This is one of the earlier peptide force fields that has seen less use with the introduction of improved methods. It uses three valence terms that are fixed, a van der Waals term, and an electrostatic term. 

The program is able to do systematic or random conformation searches using the Tripos force field. Conformation searches can include up to eight single bonds and two rings. 

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