Membrane transporters are principal players in active exchange of materials across the cellular membrane, one of the most fundamental and highly regulated processes in living cells. Investigating the molecular basis of their function, therefore, is of utmost importance in various disciplines of biological and biomedical research. These complex proteins provide highly sophisticated, operationally fine-tuned molecular machines to efficiently couple various sources of energy in the cell to vectorial translocation of various molecular species across the membrane against their chemical gradient. Investigation of the molecular details of the mechanism of membrane transporters poses a major challenge, primarily due to their structural complexity and the high dimensionality of the process of energy-dependent transport furnished by them. Substrate binding and translocation along the permeation pathway in membrane transporters is closely coupled to numerous stepwise protein conformational changes of various magnitudes that are induced and/or coordinated by the energy- providing mechanisms, e.g., binding and co-transport of protons and other ions, or binding and hydrolysis of ATP. A detailed description of the mechanism of transport in membrane transporters, therefore, relies on methods that can describe the dynamics of these processes at an atomic level. Molecular dynamics simulation remains a highly relevant approach with sufficient temporal and spatial resolutions to investigate such processes. Application of the method to membrane transporters is a very young area of research, since sufficient structural data required for such simulations has become available only recently. Furthermore, in order to describe biologically relevant events and steps involved in the function of membrane transporters, atomistic simulations of these large biomolecules on the orders of at least 0.1-1

Public Health Relevance

Membrane transporters are proteins that mediate selective transport of a wide range of materials, e.g., nutrients, hormones, and neurotransmitters, across the cellular membrane. They are essential to almost all aspects of human physiology, and their malfunction is associated with a large number of human diseases. The research proposed in this application will investigate the mechanism of function of several membrane transporters at a molecular level.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Biochemistry and Biophysics of Membranes Study Section (BBM)
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Chin, Jean
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Vermaas, Josh V; Tajkhorshid, Emad (2014) A microscopic view of phospholipid insertion into biological membranes. J Phys Chem B 118:1754-64
Ahn, Young O; Mahinthichaichan, Paween; Lee, Hyun Ju et al. (2014) Conformational coupling between the active site and residues within the K(C)-channel of the Vibrio cholerae cbb3-type (C-family) oxygen reductase. Proc Natl Acad Sci U S A 111:E4419-28
Han, Wei; Cheng, Ricky C; Maduke, Merritt C et al. (2014) Water access points and hydration pathways in CLC H+/Cl- transporters. Proc Natl Acad Sci U S A 111:1819-24
Arcario, Mark J; Mayne, Christopher G; Tajkhorshid, Emad (2014) Atomistic models of general anesthetics for use in in silico biological studies. J Phys Chem B 118:12075-86
Vermaas, Josh V; Tajkhorshid, Emad (2014) Conformational heterogeneity of ?-synuclein in membrane. Biochim Biophys Acta 1838:3107-17
Pogorelov, Taras V; Vermaas, Josh V; Arcario, Mark J et al. (2014) Partitioning of amino acids into a model membrane: capturing the interface. J Phys Chem B 118:1481-92
Kosinska Eriksson, Urszula; Fischer, Gerhard; Friemann, Rosmarie et al. (2013) Subangstrom resolution X-ray structure details aquaporin-water interactions. Science 340:1346-9
Wen, Po-Chao; Verhalen, Brandy; Wilkens, Stephan et al. (2013) On the origin of large flexibility of P-glycoprotein in the inward-facing state. J Biol Chem 288:19211-20
Kalani, Mohamad R; Moradi, Abdulvahab; Moradi, Mahmoud et al. (2013) Characterizing a histidine switch controlling pH-dependent conformational changes of the influenza virus hemagglutinin. Biophys J 105:993-1003
Mayne, Christopher G; Saam, Jan; Schulten, Klaus et al. (2013) Rapid parameterization of small molecules using the Force Field Toolkit. J Comput Chem 34:2757-70

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