Distributed computing for macromolecular crystallography.

Modern crystallographic computing is characterized by the growing role of automated structure-solution pipelines, which represent complex expert systems utilizing a number of program components, decision makers and databases. They also require considerable computational resources and regular database maintenance, which is increasingly more difficult to provide at the level of individual desktop-based CCP4 setups. On the other hand, there is a significant growth in data processed in the field, which brings up the issue of centralized facilities for keeping both the data collected and structure-solution projects.

Enhanced fold recognition using efficient short fragment clustering.

The main structure aligner in the CCP4 Software Suite, SSM (Secondary Structure Matching) has a limited applicability on the intermediate stages of the structure solution process, when the secondary structure cannot be reliably computed due to structural incompleteness or a fragmented mainchain. In this study, we describe a new algorithm for the alignment and comparison of protein structures in CCP4, which was designed to overcome SSM's limitations but retain its quality and speed. The new algorithm, named GESAMT (General Efficient Structural Alignment of Macromolecular Targets), employs the old idea of deriving the global structure similarity from a promising set of locally similar short fragments, but uses a few technical solutions that make it considerably faster.

Macromolecular complexes in crystals and solutions.

This paper presents a discussion of existing methods for the analysis of macromolecular interactions and complexes in crystal packing. Typical situations and conditions where wrong answers may be obtained in the course of ordinary procedures are presented and discussed. The more general question of what the relationship is between natural (in-solvent) and crystallized assemblies is discussed and researched.

Crystal contacts as nature's docking solutions.

The assumption that crystal contacts reflect natural macromolecular interactions makes a basis for many studies in structural biology. However, the crystal state may correspond to a global minimum of free energy where biologically relevant interactions are sacrificed in favor to unspecific contacts. A large-scale docking experiment was performed to assess the extent of misrepresentation of natural (in-solvent) protein dimers by crystal packing.

Inference of macromolecular assemblies from crystalline state.

We discuss basic physical-chemical principles underlying the formation of stable macromolecular complexes, which in many cases are likely to be the biological units performing a certain physiological function. We also consider available theoretical approaches to the calculation of macromolecular affinity and entropy of complexation. The latter is shown to play an important role and make a major effect on complex size and symmetry.

On the relationship between sequence and structure similarities in proteomics.

Motivation: The underlying assumption of many sequence-based comparative studies in proteomics is that different aspects of protein structure and therefore functionality may be linked to particular sequence motifs. This holds true if sequence similarity is sufficiently high, but in general the relationship between protein sequence and structure appears complex and is not well understood.

Results: Statistical analysis of multiple and pairwise structural alignments of protein structures within SCOP folds is performed.