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Biomedical subjects

R W Grosse-Kunstleve

Publications and source records attributed to R W Grosse-Kunstleve.

9 recordsLinked to original sources

FINDMOL: automated identification of macromolecules in electron-density maps.

Automating the determination of novel macromolecular structures via X-ray crystallographic methods involves building a model into an electron-density map. Unfortunately, the conventional crystallographic asymmetric unit volumes are usually not well matched to the biological molecular units. In most cases, the facets of the asymmetric unit cut the molecules into a number of disconnected fragments, rendering interpretation by the crystallographer significantly more difficult. The FINDMOL algorithm is designed to quickly parse the arrangement of trace points (pseudo-atoms) derived from a skeletonized electron-density map without requiring higher level prior information such as sequence information or number of molecules in the asymmetric unit. The algorithm was tested with a variety of density-modified maps computed with medium- to low-resolution data. Typically, the resulting volume resembles the biological unit. In the remaining cases the number of disconnected fragments is very small. In all examples, secondary-structural elements such as alpha-helices or beta-sheets are easily identifiable in the defragmented arrangement. FINDMOL can greatly assist a crystallographer during manual model building or in cases where automatic model building can only build partial models owing to limitations of the data such as low resolution and/or poor phases.

Algorithms↗

Numerically stable algorithms for the computation of reduced unit cells.

The computation of reduced unit cells is an important building block for a number of crystallographic applications, but unfortunately it is very easy to demonstrate that the conventional implementation of cell reduction algorithms is not numerically stable. A numerically stable implementation of the Niggli-reduction algorithm of Krivý & Gruber [Acta Cryst. (1976), A32, 297-298] is presented. The stability is achieved by consistently using a tolerance in all floating-point comparisons. The tolerance must be greater than the accumulated rounding errors. A second stable algorithm is also presented, the minimum reduction, that does not require using a tolerance. It produces a cell with minimum lengths and all angles acute or obtuse. The algorithm is a simplified and modified version of the Buerger-reduction algorithm of Gruber [Acta Cryst. (1973), A29, 433-440]. Both algorithms have been enhanced to generate a change-of-basis matrix along with the parameters of the reduced cell.

Algorithms↗

Substructure search procedures for macromolecular structures.

This paper accompanies a lecture given at the 2003 CCP4 Study Weekend on experimental phasing. The first part is an overview of the fundamentals of Patterson methods and direct methods with the audience of the CCP4 Study Weekend in mind. In the second part, a new hybrid substructure search is outlined.

Crystallography, X-Ray↗

On symmetries of substructures.

This paper accompanies a lecture given at the 2003 CCP4 Study Weekend on experimental phasing. With the audience of the CCP4 Study Weekend in mind, an overview is given of symmetries of substructures and the implications for single isomorphous replacement and single anomalous diffraction phasing procedures, as well as difference Fourier analyses. Pointers are also provided to practical tools for working with substructure symmetries.

Crystallography, X-Ray↗

Algorithms for deriving crystallographic space-group information. II. Treatment of special positions.

Algorithms for the treatment of special positions in three-dimensional crystallographic space groups are presented. These include an algorithm for the determination of the site-symmetry group given the coordinates of a point, an algorithm for the determination of the exact location of the nearest special position, an algorithm for the assignment of a Wyckoff letter given the site-symmetry group, and an alternative algorithm for the assignment of a Wyckoff letter given the coordinates of a point directly. All algorithms are implemented in ISO C++ and are integrated into the Computational Crystallography Toolbox. The source code is freely available.

Algorithms↗

Patterson correlation methods: a review of molecular replacement with CNS.

This paper presents a review of the principles of molecular replacement with the audience of the CCP4 Study Weekend in mind. A complementary presentation with animated Patterson maps is available online (http://cci.lbl.gov/-rwgk/ccp4sw2001/). The implementation of molecular-replacement methods in the Crystallography and NMR System (CNS) is presented and discussed in some detail. The three principal components are the direct rotation function, Patterson correlation refinement and the fast translation function. CNS is available online and is free of charge for academic users.

Crystallography↗

Recent developments in software for the automation of crystallographic macromolecular structure determination.

The automation of macromolecular structure determination by X-ray crystallography has long been a goal for many researchers. Recently, there have been improvements in the underlying algorithms, some of which have been implemented in software packages that deal with multiple stages of the structure determination process. These first steps towards complete automation have made X-ray crystallography more efficient.

Automation↗

A highly automated heavy-atom search procedure for macromolecular structures.

A new highly automated heavy-atom search procedure combines a fast Fourier transform translation function, Patterson superposition functions and Patterson correlation refinement. The search procedure can be applied to various native and difference Patterson maps and their statistically weighted averages. The procedure was tested with diffraction data for several crystal structures with up to 30 heavy-atom sites in the asymmetric unit and with minimum Bragg spacings ranging from 3 to 4 A. In all cases, the correct sites were found with modest computing time.

Algorithms↗

Crystallography & NMR system: A new software suite for macromolecular structure determination.

A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing structure-determination programs, the architecture of CNS is highly flexible, allowing for extension to other structure-determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a high-level hypertext markup language (HTML) user interface, task-oriented user input files, module files, a symbolic structure-determination language (CNS language), and low-level source code. Each layer is accessible to the user. The novice user may just use the HTML interface, while the more advanced user may use any of the other layers. The source code will be distributed, thus source-code modification is possible. The CNS language is sufficiently powerful and flexible that many new algorithms can be easily implemented in the CNS language without changes to the source code. The CNS language allows the user to perform operations on data structures, such as structure factors, electron-density maps, and atomic properties. The power of the CNS language has been demonstrated by the implementation of a comprehensive set of crystallographic procedures for phasing, density modification and refinement. User-friendly task-oriented input files are available for nearly all aspects of macromolecular structure determination by X-ray crystallography and solution NMR.

Computer Simulation↗