MPBuilder: A PyMOL Plugin for Building and Refinement of Solubilized Membrane Proteins Against Small Angle X-ray Scattering Data

Membrane proteins (MPs) are the target of numerous structural and functional studies in biological and medical/pharmaceutical sciences. Strategies for the high-throughput structural analysis of MPs and of their perturbations driven by ligands having potential therapeutic applications are uncommon, often requiring scaled up crystallization, electron microscopy, and nuclear magnetic resonance (NMR) efforts. Small-angle X-ray scattering (SAXS) provides a rapid means to study low resolution structures and conformational changes of native MPs in solution without cumbersome sample preparations/treatment. The method requires the MPs solubilized in an appropriate medium (eg. detergents, mixed micelles and nanodiscs) and reliable and robust models are needed to describe the relevant complexes. Here we present MPBuilder, a simple and versatile tool for the generation and refinement of all-atom MP systems in the popular software PyMOL, an environment familiar to most biologists. MPBuilder provides building capability for protein-detergent, bicelle, and lipid-scaffold (saposin nanoparticles, nanodiscs) complexes and links this to the ATSAS software package modules for model refinement and validation against the SAXS data.