@inbook{bc83959b8ac547aba6bca10d69f0880f,
title = "Microscopic Characterization of Membrane Transporter Function by In Silico Modeling and Simulation",
abstract = "Membrane transporters mediate one of the most fundamental processes in biology. They are the main gatekeepers controlling active traffic of materials in a highly selective and regulated manner between different cellular compartments demarcated by biological membranes. At the heart of the mechanism of membrane transporters lie protein conformational changes of diverse forms and magnitudes, which closely mediate critical aspects of the transport process, most importantly the coordinated motions of remotely located gating elements and their tight coupling to chemical processes such as binding, unbinding and translocation of transported substrate and cotransported ions, ATP binding and hydrolysis, and other molecular events fueling uphill transport of the cargo. An increasing number of functional studies have established the active participation of lipids and other components of biological membranes in the function of transporters and other membrane proteins, often acting as major signaling and regulating elements. Understanding the mechanistic details of these molecular processes require methods that offer high spatial and temporal resolutions. Computational modeling and simulations technologies empowered by advanced sampling and free energy calculations have reached a sufficiently mature state to become an indispensable component of mechanistic studies of membrane transporters in their natural environment of the membrane. In this article, we provide an overview of a number of major computational protocols and techniques commonly used in membrane transporter modeling and simulation studies. The article also includes practical hints on effective use of these methods, critical perspectives on their strengths and weak points, and examples of their successful applications to membrane transporters, selected from the research performed in our own laboratory.",
keywords = "Active transport, Biological systems modeling, Conformational change, Free energy calculations, Lipid bilayers, Membrane transporter, Molecular dynamics",
author = "Vermaas, {J. V.} and N. Trebesch and Mayne, {C. G.} and S. Thangapandian and M. Shekhar and P. Mahinthichaichan and Baylon, {J. L.} and T. Jiang and Y. Wang and Muller, {M. P.} and E. Shinn and Z. Zhao and Wen, {P. C.} and E. Tajkhorshid",
note = "Funding Information: This work was supported in part by the National Institutes of Health (Grants R01-GM086749, R01-GM101048, U54-GM087519, and P41-GM104601 to E.T.). We also acknowledge computing resources provided by Blue Waters, INCITE, XSEDE (grant TG-MCA06N060 to E.T.), and PSC Anton, which were instrumental for some of the simulations results presented and discussed in this article. J.V.V. acknowledges support from the Sandia National Laboratories Campus Executive Program, which is funded by the Laboratory Directed Research and Development (LDRD) Program. Sandia is a multiprogram laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the US Department of Energy's National Nuclear Security Administration under Contract No. DE-AC04-94AL85000. N.T. acknowledges support by the National Science Foundation Graduate Research Fellowship Program under Grant No. 1144245. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",
year = "2016",
doi = "10.1016/bs.mie.2016.05.042",
language = "English (US)",
series = "Methods in Enzymology",
publisher = "Academic Press Inc.",
pages = "373--428",
booktitle = "Methods in Enzymology",
address = "United States",
}