New software, OLEX2, has been developed for the determination, visualization and analysis of molecular crystal structures. The software has a portable mousedriven workflow-oriented and fully comprehensive graphical user interface for structure solution, refinement and report generation, as well as novel tools for structure analysis. OLEX2 seamlessly links all aspects of the structure solution, refinement and publication process and presents them in a single workflowdriven package, with the ultimate goal of producing an application which will be useful to both chemists and crystallographers. computer programs J. Appl. Cryst. (2009). 42, 339-341 Oleg V. Dolomanov et al. OLEX2 341

This paper describes the mathematical basis for olex2.refine, the new refinement engine which is integrated within the Olex2 program. Precise and clear equations are provided for every computation performed by this engine, including structure factors and their derivatives, constraints, restraints and twinning; a general overview is also given of the different components of the engine and their relation to each other. A framework for adding multiple general constraints with dependencies on common physical parameters is described. Several new restraints on atomic displacement parameters are also presented.

The relationship between the structure and the properties of a drug or material is a key concept of chemistry. Knowledge of the three-dimensional structure is considered to be of such...

iotbx.cifis a new software module for the development of applications that make use of the CIF format. Comprehensive tools are provided for input, output and validation of CIFs, as well as for interconversion with high-levelcctbx[Grosse-Kunstleve, Sauter, Moriarty & Adams (2002).J. Appl. Cryst.35, 126–136] crystallographic objects. The interface to the library is written in Python, whilst parsing is carried out using a compiled parser, combining the performance of a compiled language (C++) with the benefits of using an interpreted language.

.X-ray crystallography is the primarily technique used to reveal the three-dimensional structure of protein complexes that play a critical role in Structure Based Drug Design. Because of the low ratio of observed data to refi ned parameters, macromolecular crystallographic refi nement at moderate and low resolution relies heavily on the set of known amino acid geometric parameters that ensures the correct stereochemistry of the model. Available programs for macromolecular refi nement such as REFMAC, PHENIX or SHELX use simple harmonic oscillator functions to introduce stereochemistry restraints and commonly do not account for electrostatic interactions in the system. This approach inevitably masks important structural details that are often crucial to the understanding of ligand binding within the active site of the protein. To overcome these limitations and achieve a much more realistic description of the protein-ligand geometry, we replaced these stereochemistry restraints with the energy functional derived from quantum-mechanical (QM) treatment. This treatment has been demonstrated with the successful integration of the commercial DivCon ToolKit developed by QuantumBio with the popular Python-based crystallographic package PHENIX. DivCon employs semiempirical QM methods such as AM1, PM3 or PM6 and is based on the divide-and-conquer approach to evaluate the density matrix allowing linear-scaling of the QM problem. As a result, DivCon dramatically decreases the computation costs traditionally associated with QM-based methods, making the application of quantum chemistry for large protein systems feasible.We proposed a novel protocol to incorporate QM gradients and energy targets into individual ("XYZ") coordinate refi nement step in PHENIX without altering the other refi nement stages such as the bulk solvent correction or temperature factor refi nement. Furthermore, a user has a choice to use DivCon methods either for the whole structure or a selected region -a ligand and protein active site residues, for example. Based on fi ve test protein structures downloaded from Protein Data Bank (PDB) we report the detailed comparison of the conventional and QM driven refi nements. Our preliminary results indicate that incorporation of the QM function not only improves the local geometry but also reduce the R/Rfree factors. For example, the re-refi nement of a 17-residue short protein at 2 Å resolution (PDB ID 1S9Z) using the PHENIX/DivCon package indicates a number of signifi cant structural improvements as compared to the conventional PHENIX refi nement. Notably, PHENIX/DivCon compared to PHENIX alone improved the peptide bond geometry for the non-standard N terminus residue of that protein and the DivCon driven refi nement accurately represents the stereochemistry in this region. Furthermore, the QM approach results in more reasonable H-bond network throughout the protein molecule. Keywords: DivCon, phenix, refi nement MS58.P07 Acta Cryst. (2011) A67, C593Olex2 -A complete package for molecular crystallography Horst P...

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Invariom partitioning and notation are used to estimate anisotropic hydrogen displacements for incorporation in crystallographic refinement models. Optimized structures of the generalized invariom database and their frequency computations provide the information required: frequencies are converted to internal atomic displacements and combined with the results of a TLS (translation-libration-screw) fit of experimental non-hydrogen anisotropic displacement parameters to estimate those of H atoms. Comparison with TLS+ONIOM and neutron diffraction results for four example structures where high-resolution X-ray and neutron data are available show that electron density transferability rules established in the invariom approach are also suitable for streamlining the transfer of atomic vibrations. A new segmented-body TLS analysis program called APD-Toolkit has been coded to overcome technical limitations of the established program THMA. The influence of incorporating hydrogen anisotropic displacement parameters on conventional refinement is assessed.

When calculating derivatives of structure factors, there is one particular term (the derivatives of the atomic form factors) that will always be zero in the case of tabulated spherical atomic form factors. What happens if the form factors are non-spherical? The assumption that this particular term is very close to zero is generally made in non-spherical refinements (for example, implementations of Hirshfeld atom refinement or transferable aspherical atom models), unless the form factors are refinable parameters (for example multipole modelling). To evaluate this general approximation for one specific method, a numerical differentiation was implemented within the NoSpherA2 framework to calculate the derivatives of the structure factors in a Hirshfeld atom refinement directly as accurately as possible, thus bypassing the approximation altogether. Comparing wR 2 factors and atomic parameters, along with their uncertainties from the approximate and numerically differentiating refinements, it turns out that the impact of this approximation on the final crystallographic model is indeed negligible.