An automated data processing and analysis pipeline for transmembrane proteins in detergent solutions

D. Molodenskiy; H. Mertens; D. Svergun

In order to be used in this project, the ISPyB database was extended to store information on the available high-resolution structures of MPs (e.g. homologs or crystallographic models), aminoacid sequences in FASTA format and chemical formulae of the given detergent tails and heads. The latter are used for the calculation of electron densities and approximate sizes of the detergent corona in the modelling. The electron density values can also be provided directly by the user for the cases when the automatic calculations are impossible or the values are not considered to be sufficiently accurate. Depending on the amount of a priori information, the pipeline decides whether it is possible to automatically reconstruct the model and, if so, builds it utilizing either the multiphase ab initio program MONSA (27) or the hybrid modelling program MEMPROT (28) . The starting parameters for the relevant fitting procedures are evaluated based on the available data stored in ISPyB, with the hybrid approach (25) executing upon detection of a high resolution protein component. In the absence of a high resolution protein structure the ab initio reconstruction is executed utilizing information about the amino-acid sequence of the MP, chemical formula of the detergent and additional data on the other solvent/solute components to assess the shape of the PDC.