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Retrieval and characterization of protein structure relationships are instrumental in a wide range of tasks in structural biology. The classification of protein structures (COPS) is a web service that provides efficient access to structure and sequence similarities for all currently available protein structures. Here, we focus on the application of COPS to the problem of template selection in homology modeling.

Unlabelled: The database of known protein structures contains an overwhelming number of structural similarities that frequently point to intriguing biological relationships. The similarities are often difficult to spot, and once detected their comprehension needs proper visualization. Here we introduce the new concept of a Fold Space Navigator, a user interface enabling the efficient navigation through fold space and the instantaneous visualization of pairwise structure similarities., Availability: The Fold Space Navigator is accessible as a public web service at http://services.came.sbg.ac.at

Unlabelled: Progress in structural biology depends on several key technologies. In particular tools for alignment and superposition of protein structures are indispensable. Here we describe the use of the TopMatch web service, an effective computational tool for protein structure alignment, for the visualization of structural similarities, and for highlighting relationships found in protein classifications. We provide several instructive examples., Availability: TopMatch is available as a public web service at http://services.came.sbg.ac.at.

A major problem in structural biology is the recognition of errors in experimental and theoretical models of protein structures. The ProSA program (Protein Structure Analysis) is an established tool which has a large user base and is frequently employed in the refinement and validation of experimental protein structures and in structure prediction and modeling. The analysis of protein structures is generally a difficult and cumbersome exercise. The new service presented here is a straightforward and easy to use extension of the classic ProSA program which exploits the advantages of interactive web-based applications for the display of scores and energy plots that highlight potential problems spotted in protein structures. In particular, the quality scores of a protein are displayed in the context of all known protein structures and problematic parts of a structure are shown and highlighted in a 3D molecule viewer. The service specifically addresses the needs encountered in the validation of protein structures obtained from X-ray analysis, NMR spectroscopy and theoretical calculations. ProSA-web is accessible at https://prosa.services.came.sbg.ac.at.

Unlabelled: The database SCOP (Structural Classification Of Proteins) has become a major resource in bioinformatics and protein science. A particular strength of SCOP is the flexibility of its rules enabling the preservation of the many details spotted by experts in the classification process. Here we endow classic SCOP Families with quantified structural information and comment on the structural diversity found in the SCOP hierarchy., Availability: Quantified SCOP (QSCOP) is available as a public WEB service. http://services.came.sbg.ac.at.

Modifications of the amino acid sequence generally affect protein stability. Here, we use knowledge-based potentials to estimate the stability of protein structures under sequence variation. Calculations on a variety of protein scaffolds result in a clear distinction of known mutable regions from arbitrarily chosen control patches. For example, randomly changing the sequence of an antibody paratope yields a significantly lower number of destabilized mutants as compared to the randomization of comparable regions on the protein surface. The technique is computationally efficient and can be used to screen protein structures for regions that are amenable to molecular tinkering by preserving the stability of the mutated proteins.

Lipid droplets (LDs) were considered as a mere lipid storage organelle for a long time. Recent evidence suggests that LDs are in fact distinct and dynamic organelles with a specialized proteome and functions in many cellular roles. As such, LDs contribute to cellular signaling, protein and lipid homeostasis, metabolic diseases and inflammation. In line with the multitude of functions, LDs interact with many cellular organelles including mitochondria, peroxisomes, lysosomes, the endoplasmic reticulum and the nucleus. LDs are highly mobile and dynamic organelles and impaired motility disrupts the interaction with other organelles. The reduction of interorganelle contacts results in a multitude of pathophysiologies and frequently in neurodegenerative diseases. Contacts not only supply lipids for β-oxidation in mitochondria and peroxisomes, but also may include the transfer of toxic lipids as well as misfolded and harmful proteins to LDs. Furthermore, LDs assist in the removal of protein aggregates when severe proteotoxic stress overwhelms the proteasomal system. During imbalance of cellular lipid homeostasis, LDs also support cellular detoxification. Fine-tuning of LD function is of crucial importance and many diseases are associated with dysfunctional LDs. We summarize the current understanding of LDs and their interactions with organelles, providing a storage site for harmful proteins and lipids during cellular stress, aging inflammation and various disease states. [ABSTRACT FROM AUTHOR]