Abstract
Membrane protein structures are underrepresented in structural databases despite their abundance and biomedical importance. This review focuses on the novel method of site-specific infrared dichroism (SSID) combined with constraint molecular dynamics simulation, which has recently emerged as a powerful method to obtain structures of transmembrane α-helical bundles. The theory of SSID including its latest developments is reviewed with the aim to encourage widespread application of this method. This is followed by an outline of the conformational search using experimentally constraint molecular dynamics simulations. Finally a critical evaluation of recent applications, namely the Influenza M2 proton channel, the vpu ion channel of HIV-1 and the MHC-class II associated invariant chain, is conducted.
Highlights
Membrane proteins are estimated to comprise about 30% of most genomes and account for 70% of known pharmaceutical drug targets
This review will focus on the method of sitespecific infrared dichroism (SSID), which has been developed by Arkin [2,25], in combination with a conformational search protocol developed by Adams using molecular dynamics simulations [1]
attenuated total reflection (ATR)-IR spectroscopy has been extensively reviewed in the last decade [9, 17,43], we will give a short introduction into ATR as it is essential to understand site-specific dichroism (SSID)
Summary
Membrane proteins are estimated to comprise about 30% of most genomes and account for 70% of known pharmaceutical drug targets. The most promising novel methods, which have emerged during the last decade, are solid-state NMR spectroscopy and site-specific infrared dichroism in combination with molecular dynamics simulation. ATR-IR spectroscopy has been extensively reviewed in the last decade [9, 17,43], we will give a short introduction into ATR as it is essential to understand site-specific dichroism (SSID). This will be followed by a short treatment of SSID, an overview of molecular dynamics simulation with orientational constraints and applications of these methods to biological examples will be reviewed
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