CHARMM-GUI <i>Bicelle Builder</i>: An Extension of <i>Membrane Builder</i> for Modeling and Simulation of Bicelle Systems.

Abstract

Membrane mimetics, such as detergent micelles, nanodiscs, and amphipol complexes, which can provide membrane-like environments while retaining small and soluble features, have been utilized to study membrane proteins. A bicelle, composed of varying lipids and detergents, is a useful membrane mimetic because the lipid-to-detergent ratio, the <i>q</i>-value, can be adjusted to alter the properties of the aggregate, including the thickness and size of the bicelle. However, building a bicelle model for modeling and simulation studies requires nontrivial efforts, even for experts. We introduce CHARMM-GUI <i>Bicelle Builder</i>, a web-based platform that can generate various all-atom bicelle systems via a graphical user interface with all available lipids and detergents in <i>Membrane Builder</i>. To illustrate and validate <i>Bicelle Builder</i> with practical systems, we have modeled and simulated pure bicelles consisting of 1,2-dimyristoyl-<i>sn</i>-glycero-3-phosphocholine (DMPC) lipids with 1,2-dihexanoyl-<i>sn</i>-glycero-3-phosphocholine (C6DHPC) detergents and protein-bicelle complexes, composed of DMPC with C6DHPC, foscholine-10 (FOS10), and lysophosphatidylcholine-12 (LPC12) detergents. Our simulation results indicate that <i>Bicelle Builder</i> can generate reliable and robust bicelle models with and without proteins that retain DMPC bilayer characteristics. <i>Bicelle Builder</i> is expected to help researchers better understand not only bicelles themselves but also atomistic-level structures of protein-bicelle complexes that are often difficult to access through experimental approaches.