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Radboud University, 18 november 2016, Promotor : Vriend, G. Co-promotor : Joosten, R.P., Contains fulltext : 160844.pdf (publisher's version ) (Open Access), High-quality protein structure models are essential for many Life Science applications, such as protein engineering, molecular dynamics, drug design, and homology modelling. The WHAT_CHECK model validation project and the PDB_REDO model optimisation project have shown that many structure models in the Protein Data Bank can be improved by re-interpretation of the original experimental data. This thesis has added several methods to validate and optimise details of structure models including backbone angles, peptide conformations, Zinc binding sites and B-factors.

Radboud University, 18 november 2016, Promotor : Vriend, G. Co-promotor : Joosten, R.P., Contains fulltext : 160844.pdf (publisher's version ) (Open Access), High-quality protein structure models are essential for many Life Science applications, such as protein engineering, molecular dynamics, drug design, and homology modelling. The WHAT_CHECK model validation project and the PDB_REDO model optimisation project have shown that many structure models in the Protein Data Bank can be improved by re-interpretation of the original experimental data. This thesis has added several methods to validate and optimise details of structure models including backbone angles, peptide conformations, Zinc binding sites and B-factors.

Radboud Universiteit Nijmegen, 29 november 2012, Promotor : Vriend, G., Contains fulltext : 100866.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 11 april 2012, Promotor : Vriend, G., Contains fulltext : 93556.pdf (publisher's version ) (Open Access)

Radboud Universiteit Nijmegen, 29 november 2012, Promotor : Vriend, G., Contains fulltext : 100866.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 12 mei 2010, Promotor : Vriend, G., Contains fulltext : 76549.pdf (publisher's version ) (Open Access), Nearly all processes in living organisms are governed by proteins. Research questions in (medical) biology can therefore often be reduced to questions about the biochemistry of a particular protein. E.g.: “Why does Tamiflu not work against a novel influenza mutant and how should the drug be adapted to become effective again?”. Answering such questions requires an accurate and detailed structural description of the protein under investigation in which each individual protein atom has three-dimensional (3D) coordinates. These 3D structures of proteins are typically determined using X-ray crystallography which is difficult and labour intensive. As a result, we know far fewer protein structures than actual proteins. To advance our scientific knowledge we have to make do with the structures currently available. In this thesis three bioinformatics approaches to get the most out of current structures are explored. The first approach is structure validation which uses (statistical) knowledge of molecules and chemical interactions to detect good, bad, and ugly parts of protein structures. This helps to select the optimal protein structure to answer specific research questions and helps to estimate the reliability of scientific conclusions drawn from protein structures. The second approach is improving the quality of current structures. Not by completely repeating the X-ray crystallography experiments, but by using the original experimental data and the latest computational methods. We explore this in depth with a proof-of-concept experiment followed by a high throughput computational experiment on 17,000 structures and an evaluation of what structural elements can be improved by actively fixing errors in structures. The third and most constructive approach is making new protein structures via homology modelling. We discuss the importance of combining wet-lab and computational protein science and show that homology modelling depends on high-quality protein structures as a sta

RU Radboud Universiteit Nijmegen, 05 oktober 2007, Promotor : Vriend, G., Contains fulltext : 30962.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 05 oktober 2007, Promotor : Vriend, G., Contains fulltext : 30962.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 09 februari 2006, Promotores : Vriend, G., Vuister, G.W., Contains fulltext : 27386.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 28 november 2005, Promotores : Vriend, G., Brunner, H.G. Co-promotor : Leunissen, J.A.M., Contains fulltext : 33210.pdf (publisher's version ) (Open Access), Disease gene identification based on chromosomal localisation is sometimes difficult and often time-consuming. It requires collecting as much information on the disease as possible. Combining positional information with disease characteristics might give hints by which candidate disease genes can be selected. Our hypothesis was that internet databases, which contain gene specific data as well as databases that contain phenotype descriptions, can be utilized systematically for identification of disease genes. We present two bioinformatics strategies that are able to identify human candidate disease genes and classify human disease phenotypes.Phenotype analysis is equally relevant to disease gene identification as it is to the functional annotation of the human genome: Over the course of the coming years major improvements are to be expected with regard to gene identification methods for monogenic, and multifactorial diseases, mutation detection, and various methods for cross-species comparisons. Bioinformatics approaches such as those described here, should be a useful addition to sequence and gene-based analyses. While much remains to be discovered from systematic phenotype-genotype analyses, an essential prerequisite will be the development of a standardized and internationally agreed nomenclature for phenotype definition that is applicable to humans as well as to the major model organisms that are in use today.

RU Radboud Universiteit Nijmegen, 27 september 2004, Promotor : Vriend, G., Contains fulltext : 19506_lastmioft.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 27 september 2004, Promotor : Vriend, G., Contains fulltext : 19506_lastmioft.pdf (publisher's version ) (Open Access)

RU Radboud Universiteit Nijmegen, 27 september 2004, Promotor : Vriend, G., Contains fulltext : 19506_lastmioft.pdf (publisher's version ) (Open Access)