Advances in protein and small-molecule charge-density refinement methods using MoPro

With an increasing number of biological macromolecule structures solved at ultra-high resolution and with the advances of supramolecular chemistry, it becomes necessary to extend to large systems experimental charge-density study methods that are usually applied to small molecules. The latest developments in the refinement program MoPro ( Molecular Properties), dedicated to the charge-density refinement at ( sub) atomic resolution of structures ranging from small molecules to biological macromolecules, are presented. MoPro uses the Hansen & Coppens [ Acta Cryst. ( 1978), A34, 909 - 921] multipolar pseudo-atom model for the electron-density refinement. Alternative methods are also proposed, such as modelling bonding and lone-pair electron density by virtual spherical atoms. For proteins at atomic resolution, a charge-density database developed in the laboratory enables the transfer of multipolar parameters. The program allows complex refinement strategies to be written and has numerous restraints, constraints and analysis tools for use in the structure and electron-density analysis. New kappa and multipolar parameter restraints/constraints are also implemented and discussed. Furthermore, constraints on the electron density, such as local symmetry and atom equivalence, are easily defined. Some examples of applications, from small molecules to large unit cells ( including the enzyme aldose reductase), are given in order to guide the MoPro user and to show the large field of applicability of this code.