Biomedical subjects

W A Koppensteiner

Publications and source records attributed to W A Koppensteiner.

7 recordsLinked to original sources

PubMed2000

The role of protein structure in genomics.

The genome projects produce an enormous amount of sequence data that needs to be annotated in terms of molecular structure and biological function. These tasks have triggered additional initiatives like structural genomics. The intention is to determine as many protein structures as possible, in the most efficient way, and to exploit the solved structures for the assignment of biological function to hypothetical proteins. We discuss the impact of these developments on protein classification, gene function prediction, and protein structure prediction.

Databases, Factual↗

PubMed2000

Characterization of novel proteins based on known protein structures.

The genome sciences face the challenge to characterize structure and function of a vast number of novel genes. Sequence search techniques are used to infer functional and structural information from similarities to experimentally characterized genes or proteins. The persistent goal is to refine these techniques and to develop alternative and complementary methods to increase the range of reliable inference.Here, we focus on the structural and functional assignments that can be inferred from the known three-dimensional structures of proteins. The study uses all structures in the Protein Data Bank that were known by the end of 1997. The protein structures released in 1998 were then characterized in terms of functional and structural similarity to the previously known structures, yielding an estimate of the maximum amount of information on novel protein sequences that can be obtained from inference techniques. The 147 globular proteins corresponding to 196 domains released in 1998 have no clear sequence similarity to previously known structures. However, 75 % of the domains have extensive structure similarity to previously known folds, and most importantly, in two out of three cases similarity in structure coincides with related function. In view of this analysis, full utilization of existing structure data bases would provide information for many new targets even if the relationship is not accessible from sequence information alone. Currently, the most sophisticated techniques detect of the order of one-third of these relationships.

Amino Acid Sequence↗

PubMed2000

ProSup: a refined tool for protein structure alignment.

We investigated and optimized a method for structure comparison which is based on rigid body superimposition. The method maximizes the number of structurally equivalent residues while keeping the root mean square deviation constant. The resulting number of equivalent residues then provides an adequate similarity measure, which is easy to interpret. We demonstrate that the approach is able to detect remote structural similarity. We show that the number of equivalent residues is a suitable measure for ranking database searches and that the results are in good agreement with expert knowledge protein structure classification. Structure comparison frequently has multiple solutions. The approach that we use provides a range of alternative alignments rather a single solution. We discuss the nature of alternative solutions on several examples.

Algorithms↗

PubMed1999

An attempt to analyse progress in fold recognition from CASP1 to CASP3.

The Critical Assessment of Techniques for Protein Structure Prediction (CASP) experiment has been conducted for the third time. An obvious question is whether there has been progress from CASP1 to CASP3. An analysis depends on many variables, including prediction category, number and difficulty of targets, methods used to evaluate prediction success, and the rules for submission. It also depends on whether progress is measured in terms of all predictions submitted or in terms of the best predictions for each target. The progress made by individual groups is another interesting issue. In view of this complexity and the limited amount of data, an objective estimate of progress is difficult to obtain. Despite such difficulties, some estimate of progress is desirable. Here, we present an attempt to quantify progress in the fold-recognition category from CASP1 to CASP3. The numbers indicate clear progress from CASP1 to CASP2 but no improvement from CASP2 to CASP3. However, we argue that the targets in CASP3 are more difficult compared with CASP2, which translates into better performance of CASP3 over CASP2.

Autoantigens↗

PubMed1999

Automated large scale evaluation of protein structure predictions.

Evaluation and assessment are critical issues in CASP experiments. Automated procedures are necessary to compare a large number of predictions with the target folds. The evaluation has to reveal the maximum extent of similarity between predictions and targets, it should be applicable across prediction categories, and it should be transparent and accessible to a wide community. Here we present an automated evaluation scheme which is an attempt to meet these requirements. In the implementation and execution of this scheme we had to solve or circumvent problems of convergence, where algorithms fail to find optimum solutions, problems of ambiguity where no unique optimum solution exists, and problems in ranking and interpretation. Key features of this implementation are (1) the root mean square deviation of structure superimposition is kept close to a constant value throughout the evaluation and (2) all structural matches found between two folds are taken into account. We discuss these points in detail and describe the numerical criteria used in the CASP3 evaluation.

Algorithms↗

PubMed1999

Sustained performance of knowledge-based potentials in fold recognition.

We describe the results obtained using fold recognition techniques in our third participation in the CASP experiment. The approach relies on knowledge-based potentials for alignment production and fold identification. As indicated by the increase in alignment quality and fold identification reliability, the predictions improved from CASP1 to CASP3. In particular, we identified structural relationships in which no known evolutionary link exists. Our predictions are based on single sequences rather than multiple sequence alignments. Additionally, we voluntarily submitted only a single model for each target because, in our view, submission of a single model is the most stringent test. We describe the methods used, the strategy adopted in the predictions, and the prediction results and discuss future work.

Algorithms↗

PubMed1998

Knowledge-based potentials--back to the roots.

Applications of knowledge-based quantities in protein structure theory are well established but their theoretical foundation, physical interpretation, and range of applicability seems unclear or even controversial. Moreover, the current literature contains terms like "pseudo-energy", "energy-like quantity", or "true energy" which are vague and unclear and terms like "mean-force potential" corresponding to well defined concepts. Seemingly contradictory results are often caused by inconsistent terminology. Often such problems are resolved when the physical nature of the involved quantities is properly defined. We summarize the fundamental principles of mean-force potentials and radial distribution functions as defined in statistical mechanics and put these into perspective with the term "knowledge-based potential".

Databases, Factual↗