Memprotmd: Protein-Lipid Interactions of Phospholipid Biosynthetic Enzymes and Development of the Web Database

Abstract

Membrane bound proteins play an important role in many biological processes, therefore understanding their structure and function represents an important scientific challenge. Whilst improvements in experimental techniques are revealing high resolution structures for an increasing number of membrane proteins, these structures are rarely resolved in complex with membrane lipids. The MemProtMD pipeline uses Coarse-Grained molecular dynamics simulations to allow a lipid bilayer to self-assemble around a membrane protein, and can be used to study the structure and dynamics of membrane proteins and lipids at both Coarse-Grained and atomistic representations.A web database (http://sbcb.bioch.ox.ac.uk/memprotmd/beta/) has been developed to make data generated by the MemProtMD pipeline available to the scientific community. Simulations and the results of subsequent analysis can be viewed using a web browser, including interactive 3D visualisations of the assembled bilayer and 2D visualisations of membrane protein topology and lipid contact data. All files required to run further coarse-grained or atomistic simulations of proteins in the database are provided. Proteins may be searched using keywords or browsed using classification systems such as MPStruc or the Transporter Classification Database.Phospholipid biosynthetic enzymes catalyse reactions involving membrane lipids and often interact with membrane lipids in unusual ways. Many of these interactions are important to the biological function of the enzyme and can be identified using the MemProtMD pipeline. Tools provided through the MemProtMD web database were used to examine the properties of the phospholipid biosynthetic enzymes diacylglycerol kinase, phosphatidate cytidylyltransferase and acyl-CoA desaturase when simulated in a membrane environment.