General information

The groups of Vuister/Vriend develop methodology for improved structure generation and validation. In addition, the group of Geerten Vuister focuses on proteins domains involved in the regulation of ion transport and the regulation and assembly of active biological complexes, using high-resolution NMR and X-ray crystallography in conjunction with other biophysical techniques, such as isothermal titration calorimetry and surface-plamon resonance.
The Vuister group is part of the Institute for Molecules and Materials of the Radboud University Nijmegen. The Vriend group of the CMBI is part of the Nijmegen Center for Molecular life Sciences, a research centre of the Radboud University Medical Centre.The CMBI hosts NBIC and the national cheminformatics consortium.

Research

Research of the Vuister group concern the following topics:

• CING: Validation of NMR structures
•  Regulation of Ca-transport across membranes: Ca²⁺ ions are crucial in many cellular processes, including neuronal response, muscle contraction, enzyme activity, gene transcription, cell death, proliferation and differentiation. We study ion transport across the membrane from a structural- and biophysical perspective, with the aim to explain biological functioning. In particular, we focus on the regulatory mechanisms that govern Ca²⁺ fluxes across membranes. Specific systems currently involve the Na⁺/Ca²⁺-exchanger (NCX), a highly ubiquitous ion transporter that constitutes the dominant Ca²⁺ efflux mechanism in heart and sensory neurons and the Na⁺/K⁺-ATPase, an ion transporter functionally connected to the NCX. 

• Assembly of active biomolecular complexes: Protein interaction domains play essential roles in the transport, localization, assembly and functioning of multi-protein complexes. We study the structure function relationships of the five PDZ domains of the protein tyrosine phosphatase PTP-BL and the so-called PAH domains of the transcriptional co-repressor SIN3.

• Methodology: In this project we focus upon methods to improve NMR-derived structures, develop automated tools for structure quality assessment and data evaluations, and design new NMR sequences for the study of dynamics and interactions.

Research of the Vriend group works concerns the following topics:

• Homology modelling technology and applications.
• Structure validation and structure determination improvement.
• Molecular class specific information systems (like the GPCRDB or the NucleaRDB).
• Data mining.
• WHAT IF molecular modelling and visualization software.
  

Structure validation tutorial.

We developped a Structure validation tutorial to work with the tools that can assist you in finding unlikely elements in your data and structure ensembles. In four exercises we will provide you with an overview how to validate your data and resulting NMR ensembles, and improve your results. Each exercise targets a specific aspect in the validation process.

Software

Information concerning software developed by the groups can be found here and here.

Relevant publications

• Nabuurs, S.B., Spronk, C.A.E.M, Krieger, E., Maassen, H., Vriend, G. & Vuister, G.W. (2003) “Quantitative evaluation of experimental NMR restraints”, J. Am. Chem. Soc.125, 12026-12034. 
• Nabuurs, S.B., Nederveen, A.J., Vranken, W., Doreleijers, J.F., Bonvin, A.M.J.J., Vuister, G.W., Vriend, G. & Spronk, C.A.E.M. (2004) "DRESS, a Database of REfined Solution nmr Structures", Proteins, Struct., Func., Genet. 45, 483-486. 
• Spronk, C.A.E.M., Nabuurs, S.B., Vriend, G. & Vuister, G.W. (2004) “Validation of High-Resolution NMR-Structures”, Prog. NMR Spectr. 45, 315-337. 
• Nabuurs, S, Krieger, E., Spronk, C.A.E.M., Nederveen, A.J, Vriend, G., & Vuister, G.W. (2005) “Definition of a new information-based per-residue quality parameter”, J. Biomol. NMR 33, 123-134. 
• Nabuurs, S, Spronk, C.A.E.M., Vuister, G.W. & Vriend, G. (2006) “Traditional Biomolecular Structure Determination by NMR Spectroscopy Allows for Major Errors”, PLoS Comput. Biol. 2, e9.

Workpackages

Partner 4 is involved in work packages 2 and 5, and in workpackage 3.