Peptide-Based Drug Design

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Molecular Dynamics Simulations of Peptides
Jeffrey Copps, Richard F. Murphy, and Sandor Lovas
Key Words: Force field; Molecular dynamics; simulations; replica exchange;
GROMACS; GROMOS96; folding; secondary structure
1. Introduction
Molecular dynamics (MD) simulations fill a significant niche in the study
of chemical structure. While nuclear magnetic resonance (NMR) yields
the structure of a molecule in atomic detail, this structure is the timeaveraged
composite of several conformations. Electronic and vibrational circular
dichroism spectroscopy and more general ultraviolet/visible and infrared (IR)
spectroscopy yield the secondary structure of the molecule, but at low resolution.
MD simulations, on the other hand, yield a large set of individual structures
in high detail and can describe the dynamic properties of these structures in
solution. Movement and energy details of individual atoms can then be easily
obtained from these studies.
In MD simulations, trajectories (configurations as a function of time)
of individual atoms are generated by simultaneous integration of Newton’s
equation of motion. The forces acting on each atom are the negative derivative
of the potential energy and are termed the “force field.” Force fields are
parametrized using physical data from x-ray crystallography, IR and Raman
spectroscopy, as well as high-level quantum mechanical calculations with model
compounds, to reproduce the vibrational and conformational characteristics of
a wide variety of molecules. The potential energy is the sum of bond and angle
energies, the energy of bond rotations, and the energy of nonbonded van der
Waals and electrostatic interactions, as in the general class I force field equation
From: Methods in Molecular Biology, vol. 494: Peptide-Based Drug Design
Edited by: L. Otvos, DOI: 10.1007/978-1-59745-419-3 7, © Humana Press, New York, NY
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