Experiences with applications of macromolecular tools in supramolecular crystallography

Abstract

Supramolecular structures, with ever increasing size ranging from a few up to tens of nanometres, represent an intermediate stage between small molecules and biological macromolecules. Many crystal structures of these large supramolecular assemblies have been solved using dual space algorithms. However, supramolecular assemblies with a capsular shape present a particular challenge for crystallography, especially when they are chiral and composed of only light atoms. In this paper, we show that the application of “routine” macromolecular tools may be of great help in solving the crystal structures of supramolecular assemblies that are otherwise refractory to the routine methods of small molecule crystallography. Specifically, we have applied the method of molecular replacement as implemented in PHASER in order to solve the crystal structure of a chiral organic capsule, which could not be determined using direct or dual space methods. By utilizing various models consisting of well-defined supramolecular “bricks” or modelled structures, we show how model size (fraction of the asymmetric unit) and quality (root mean square deviation from target) influence the success rate of medium sized non-protein structures. The results indicate that supramolecular structures, that are still “small molecules” for macromolecular standards, can be successfully solved using even very small models, down to 25% by weight of the contents of the asymmetric unit.