Introduction to Molecular Dynamics: Theory and Applications in Biomolecular Modeling - Computational Modeling of Biological Systems - page 24

which allows the simultaneous evaluation of the binding free energy for multiple
ligands. Interested readers can find more discussions of these methods in the
corresponding research articles.
So far, all the methods discussed here are based on equilibrium MD simulations.
With recent theory advancement in nonequilibrium statistical mechanics [ 28 , 59 ], we
can also calculate free energy changes using nonequilibrium simulations. This type
of method is based on the Jarzynski equality [ 58 , 59 ], and can be combined with the
steered molecular dynamics (SMD) simulation [ 57 , 93 ] technique to produce free
energy profiles along a reaction coordinate.

7 Outlook

In this chapter, we have discussed the various theoretical aspects of MD and
provided examples of its recent applications on biomolecular systems. Compared
with the first MD simulation on a protein [ 87 ], which lasted about 9 ps, the
development of MD has come a long way. The method has made significant
contributions to our understanding of the behaviors of complex biomolecules.
Today, with the power of supercomputers and the progress of MD softwares, we
can readily perform simulations on millions of atoms for tens to hundreds of
nanoseconds. The recent launch of specialized machines [ 103 , 104 ] and the usage of
graphics processing units (GPUs) [ 108 , 125 ] have initiated a new round of exciting
method advancement. With these new technologies, we can expect MD simulations
to make even more significant contributions to our understanding of biomolecular
systems in future.

Acknowledgments This work has been supported in part by the National Science Foundation, the
National Institutes of Health, Howard Hughes Medical Institute, Center for Theoretical Biological
Physics, the National Biomedical Computation Resource, and the NSF supercomputer centers.

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