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Biomedical subjects

Frank Wien

Publications and source records attributed to Frank Wien.

4 recordsLinked to original sources
PubMed2006

A reference database for circular dichroism spectroscopy covering fold and secondary structure space.

MOTIVATION: Circular Dichroism (CD) spectroscopy is a long-established technique for studying protein secondary structures in solution. Empirical analyses of CD data rely on the availability of reference datasets comprised of far-UV CD spectra of proteins whose crystal structures have been determined. This article reports on the creation of a new reference dataset which effectively covers both secondary structure and fold space, and uses the higher information content available in synchrotron radiation circular dichroism (SRCD) spectra to more accurately predict secondary structure than has been possible with existing reference datasets. It also examines the effects of wavelength range, structural redundancy and different means of categorizing secondary structures on the accuracy of the analyses. In addition, it describes a novel use of hierarchical cluster analyses to identify protein relatedness based on spectral properties alone. The databases are shown to be applicable in both conventional CD and SRCD spectroscopic analyses of proteins. Hence, by combining new bioinformatics and biophysical methods, a database has been produced that should have wide applicability as a tool for structural molecular biology.

Algorithms↗
PubMed2004

Biomedical applications of synchrotron radiation circular dichroism spectroscopy: identification of mutant proteins associated with disease and development of a reference database for fold motifs.

Synchrotron radiation circular dichroism (SRCD) spectroscopy is an emerging technique in structural biology with particular value for accurate secondary structure determination, monitoring protein folding and kinetics, and drug discovery. This paper discusses new biomedical applications of SRCD, notably the identification of conformational changes associated with a mutant protein that causes disease, and the development of methods for identification of fold motifs in the context of structural genomics programmes. In addition, it presents for the first time, very low wavelength (below 154 nm) data for a protein in aqueous solution, demonstrating the presence of heretofore-unseen electronic transitions.

Animals↗
PubMed2002

Database searching for thymidine and thymidylate kinase inhibitors using three-dimensional structure-based methods.

Structure-based drug design methods were used to search for novel inhibitors of herpes simplex virus type 1 (HSV-1) thymidine kinase and Mycobacterium tuberculosis thymidylate kinase. The method involved the use of crystal structure complexes to guide database searching for potential inhibitors. A number of weak inhibitors of HSV-2 were identified, one of which was found to inhibit HSV-1 TK and HSV-1 TK-deficient viral strains. Each compound tested against M. tuberculosis thymidylate kinase was found to have some activity. The best of these compounds was only 4.6-fold less potent than 3'-azido-3'-deoxythymidine-5'-monophosphate (AZTMP). This study demonstrates the utility of structure-based drug design methods in the search for novel enzyme inhibitors.

Anti-Bacterial Agents↗