Molecular Modeling of Neuropeptides

Abstract

Molecular modeling is the science of the generation, manipulation, and representation of three-dimensional structures of molecules using computational chemistry and high resolution computer graphics. Since peptides of biological interest are large molecules, molecular mechanics (MM) (1) is used almost exclusively as a computational tool. Molecular mechanics is a nonquantum method for calculating molecular properties that do not depend on electronic effects. The forces acting on the atoms in a molecule are described in terms of a set of classical potential functions such as harmonic oscillators, Morse potentials, and Lennard-Jones potentials. Parameters of these functions are usually obtained from experimental structural and thermodynamic studies of model molecules. A set of equations together with then parameters is called a force field. Separate potential functions are used to calculate bond stretching, angle bending, bond twisting, and nonbonded interactions such as van der Waals and electrostatic interactions. Molecular mechanics methods reproduce experimental results well if the compound being examined is similar to those used to create the parameters. Consequently, several force fields have been developed for computations on peptides, including CHARMM (2), AMBER (3), DISCOVER (4), GROMOS (5, and ECEPP (6). The performance of the different force fields in their application to peptides and proteins, however, should be evaluated on the basis of published data. Commercially available molecular modeling packages implement one of these force fields. The computational procedure described below was carried out using the SYBYL 6.1 (7) package in which the AMBER force field was implemented.