Biomedical subjects

Manfred J Sippl

Publications and source records attributed to Manfred J Sippl.

5 recordsLinked to original sources

PubMed2006

QSCOP--SCOP quantified by structural relationships.

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.

Computer Simulation↗

PubMed2006

NQ-Flipper: validation and correction of asparagine/glutamine amide rotamers in protein crystal structures.

The error rate of asparagine (Asn) and glutamine (Gln) amide rotamers in protein crystal structures is in the order of 20% and as a consequence the current Protein Database (PDB) contains approximately half a million incorrect Asn and Gln side-chain rotamers. Here we present NQ-Flipper, a web service based on knowledge-based potentials of mean force to automatically detect and correct erroneous rotamers. We achieve excellent agreement with expert curated data.

Asparagine↗

PubMed2006

Self-consistent assignment of asparagine and glutamine amide rotamers in protein crystal structures.

The current protein structure database contains unfavorable Asn/Gln amide rotamers in the order of 20%. Here, we derive a set of self-consistent potential functions to identify and correct unfavorable rotamers. Potentials of mean force for all heavy atoms are compiled from a database of high-resolution protein crystal structures. Starting from erroneous data, a refinement-correction cycle quickly converges to a self-consistent set of potentials. The refinement is entirely driven by the deposited structure data and does not involve any assumptions on molecular interactions or any artificial constraints. The refined potentials obtained in this way identify unfavorable rotamers with high confidence. Since the state of Asn/Gln rotamers is largely determined by hydrogen bond interactions, the features of the respective potentials are of interest in terms of molecular interactions, protein structure refinement, and prediction. The Asn/Gln rotamer assignment is available as a public web service intended to support protein structure refinement and modeling.

Amides↗

PubMed2004

Protein sequence randomization: efficient estimation of protein stability using knowledge-based potentials.

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.

Amino Acid Sequence↗

PubMed2004

WILMA-automated annotation of protein sequences.

Large-scale annotation of sets of proteins is a frequently occurring task in association with genome sequencing projects. Here, we present an automated platform for the functional annotation of large sets of protein sequences. Various bioinformatics tools are used to achieve a comprehensive description of protein sequences and to link these results to standard Gene Ontology descriptors for molecular function, biological processes and cellular components. Access to the annotation is provided via a web-interface and database queries. These interfaces allow to formulate proteome wide queries as well as the investigation of details of individual results. WILMA annotations of the proteomes of Homo sapiens, Mus musculus, Arabidopsis thaliana and Caenorhabditis elegans are accessible at http://www.came.sbg.ac.at/wilma/

Amino Acid Sequence↗