334 8.2 Molecular Simulation Methods
8.2.9 SOFTWARE AND HARDWARE FOR MD
Software evolves continuously and rapidly, and so this is not the right forum to explore all
modern variants of MD simulation code packages; several excellent online forums exist that
give up-to-date details of the most recent advances to these software tools, and the interested
reader is directed to these. However, a few key software applications have emerged as having
significant utility in the community of MD simulation research, whose core features have
remained the same for the past few years, which are useful to discuss here. Three leading soft
ware applications have grown directly out of the academic community, including Assisted
Model Building with Energy Refinement (AMBER, developed originally at the Scripps
Research Institute, United States), Chemistry at HARvard Macromolecular Mechanics
(CHARMM developed at the University of Harvard, United States), and GROningen
MAchine for Chemical Simulations (GROMACS, developed at the University of Gröningen,
the Netherlands).
The term “AMBER” is also used in the MD community in conjunction with “force fields” to
describe the specific set of force fields used in the AMBER software application. AMBER soft
ware uses the basic force field of Equation 8.14, with presets that have been parameterized for
proteins or nucleic acids (i.e., several of the parameters used in the potential energy approxi
mation have been preset by using prior QM simulation or experimental biophysics data for
these different biomolecule types). AMBER was developed for classical MD, but now has
interfaces that can be used for ab initio modeling and hybrid QM/MM. It includes implicit
solvent modeling capability and can be easily implemented on graphics processor units
(GPUs, discussed later in this chapter). It does not currently support standard Monte Carlo
methods but has replica exchange capability.
CHARMM has much the same functionality as AMBER. However, the force field used has
more complexity, in that it includes additional correction factors:
(8.27)
U
k
U
k
u
u
impropers
impropers
W
eq
U
B
Urey
Bradley
u
eq
=
=
−
(
)
−
(
)
∑
∑
−
−
ω
ω
2
2
The addition of the impropers potential (Uimpropers) is a dihedral correction factor to compen
sate for out-of-plane bending (e.g., to ensure that a known planar structural motif remains
planar in a simulation) with kω being the appropriate impropers stiffness and ω is the out-
of-pane angle deviation about the equilibrium angle ωeq˙ The Urey–Bradley potential (UU-B)
corrects for cross-term angle bending by restraining the motions of bonds by introducing a
virtual bond that counters angle bending vibrations, with u a relative atomic distance from
the equilibrium position ueq. The CHARMM force field is physically more accurate than that
of AMBER, but at the expense of greater computational cost, and in many applications, the
additional benefits of the small correction factors are marginal.
GROMACS again has many similarities to AMBER and CHARMM but is optimized for
simulating biomolecules with several complicated bonded interactions, such as biopolymers
in the form of proteins and nucleic acids, as well as complex lipids. GROMACS can operate
with a range of force fields from different simulation software including CHARMM, AMBER,
and CG potential energy functions; in addition, its own force field set is called Groningen
molecular simulation (GROMOS). The basic GROMOS force field is similar to that of
CHARMM, but the electrostatic potential energy is modeled as a Coulomb potential with
reaction field (UCRF), which in its simplest form is the sum of the standard ~1/rij Coulomb
potential (UC) with additional contribution from a reaction field (URF), which represents the
interaction of atom i with an induced field from the surrounding dielectric medium beyond
a predetermined cutoff distance Rrf due to the presence of atom j: