Abstract
A necessary step prior to starting any membrane protein computer simulation is the creation of a well-packed configuration of protein(s) and lipids. Here, we demonstrate a method, alchembed, that can simultaneously and rapidly embed multiple proteins into arrangements of lipids described using either atomistic or coarse-grained force fields. During a short simulation, the interactions between the protein(s) and lipids are gradually switched on using a soft-core van der Waals potential. We validate the method on a range of membrane proteins and determine the optimal soft-core parameters required to insert membrane proteins. Since all of the major biomolecular codes include soft-core van der Waals potentials, no additional code is required to apply this method. A tutorial is included in the Supporting Information.
Highlights
Membrane proteins are crucial players in a wide range of important cellular processes, from signaling to controlling the movement of ions and molecules into and out of cells; over 60% of drug targets are membrane proteins.[1]. They are categorized depending on the strength and nature of their interaction with the cell membrane: peripherial membrane proteins (PMPs) bind only transiently to cell membranes, whereas integral membrane proteins (IMPs) are firmly inserted into the cell membrane
Computer simulation of membrane proteins has proven to be a useful counterpart to experiment.[2−4] The first membrane protein molecular dynamics (MD) simulation was run 30 years ago[5] and comprised a single gramicidin channel surrounded by 16 DMPC lipids
We investigated the effect of modifying α and N since these can be varied in all of the major molecular dynamics codes; a and c cannot, so they are assumed to be 1 and 6 throughout
Summary
Membrane proteins are crucial players in a wide range of important cellular processes, from signaling to controlling the movement of ions and molecules into and out of cells; over 60% of drug targets are membrane proteins.[1]. Examining these two metrics will be our basis for proposing a set of alchembed parameters that will allow any membrane protein to be inserted into an arrangement of lipids, using either an atomistic or a coarse-grained force field.
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