Noah Trebesch, Josh V. Vermaas, and Emad Tajkhorshid.
Computational characterization of molecular mechanisms of membrane
transporter function.
In Carmen Domene, editor, Computational Biophysics of Membrane
Proteins, chapter 7, pp. 197-236. Royal Society of Chemistry, Cambridge,
UK, 2017.
TREB2016-ET
Transport of materials across the cellular membrane is a fundamental process in biology.
Active membrane transporters constitute one of the major classes of proteins that mediate
this process, and they do so in a highly regulated and selective manner. In order to transport
substrates uphill, these molecular machines rely on a diverse spectrum of conformational
changes spanning multiple time and size scales, and they couple these motions to various
sources of energy, including transmembrane electrochemical gradients and ATP hydrolysis.
Computational techniques such as molecular dynamics simulations and free energy
calculations provide us with a powerful repertoire of biophysical tools offering unparalleled
spatial and temporal resolutions that complement experimental methodologies and help us
understand the molecular basis of function in membrane transporters. In this chapter, we
present an overview of a number of examples of recent studies performed in our own lab in
which computational methods and simulation techniques have been successfully employed
to investigate and to characterize the microscopic molecular events that underlie membrane
transporter function. While highlighting a number of recent approaches developed
specifically to tackle challenging problems in membrane transporters, e.g., characterizing
the nature of large-scale conformational changes, the presented studies also provide
examples of a variety of mechanistically interesting and biologically important transporter
systems.
