The French National Research Agency Projects for science

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ANR funded project

JCJC - SVSE 5 - Physique, chimie du vivant et innovations biotechnologiques (JCJC SVSE 5)
Edition 2011


HYDROSAS


Modelling of protein hydration water for small-angle scattering

Modeling of protein hydration water
The knowledge of atomic structures of biomacromolecular complexes is essential to understand life at a molecular level. To this end combined approaches (crystallography/NMR with electron microscopy and/or small angle scattering) have been developed recently. In these combined approaches the quality and accuracy of atomic models depends on the influence of the hydration shell surrounding the molecules.

Description of the protein hydration shell as a function of their physico-chemical properties
This ANR project aims at developing an accurate description of the protein hydration shell. The experimental results will be compared with existing software and, if needed, new programs will be developed for the scientific community.

Protein hydration shell as a function of their physico-chemical properties by a combined SAXS/SANS approach
The project aims at studying the structural properties of protein hydration shells as a function of their physico-chemical properties by small angle X-ray and neutron scattering (SAXS/SANS). Both probes see atoms differently (different contrast between proteins and water) and can distinguish the density fluctuations of the water in the proximity of the proteins.

Results

The project is in its initial phase (6 months) with the first experiments being carried out.

Outlook

An improved description of the protein hydration shell will allow to determine structures of biomacromolecular complexes with more accuracy and understand their function at a molecular level.

Scientific outputs and patents

The project is in its initial phase (6 months) with the first experiments being carried out.

Partners

IBS CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE RHONE-ALPES SECTEUR ALPES

ANR grant: 256 162 euros
Beginning and duration: juillet 2011 - 36 mois

Submission abstract

This ANR JCJC proposal aims at understanding and describing the contribution of protein hydration water in bio-macromolecular modelling approaches that use small angle X-ray or neutron scattering (SAXS/SANS) in combination with high-resolution models from the subunits composing the complex. We propose a systematic and detailed study by recording SAXS and SANS data from three protein families that vary in size, oligomeric state and surface charge properties and to evaluate the respective contribution of hydration water with respect to the atomic structures only. The final objective of this ANR JCJC is to correlate the hydration water contributions to the molecular properties of the systems studied (surface/volume ratio, surface properties,…) and develop a computer program that can calculate and anticipate these contributions for any protein molecule (or protein complex) studied in a more accurate and general way than with currently available programs.

The latest generation of model-building programs uses SAXS/SANS data in combination with information from atomic-resolution techniques (NMR or crystallography). These programs are very ambitious and aim at proposing pseudo-atomic models of bio-macromolecular complexes. However, one of the limiting factors in the accuracy of pseudo-atomic models provided by combining high-resolution structures with small angle scattering data is the influence/contribution of the hydration water to the scattering curve. Only a handful of international groups are working on this topic at the moment.

Many flexible and high molecular weight bio-macromolecular complexes with important functions in translation, transcription and signal transduction are only difficultly accessible by either NMR or crystallography alone. Approaches combining these high-resolution techniques with small-angle scattering restraints are therefore increasingly used to address the function and structural biology of these systems and will probably become even more important over the next 10 years. It is therefore of great interest to provide accurate structural tools for the large community working with these systems.

The project and consortium proposed are in a unique position in France to contribute significantly to the development of model-building approaches in small-angle scattering for several reasons: i) the coordinator is an internationally renowned specialist of small-angle scattering and has contributed to the methodological development of SAXS/SANS approaches in combination with NMR, ii) the protein systems to be studied are excellently suited to produce a systematic data set of scattering curves that vary as a function of their structural properties, iii) the protein systems are excellently characterized, their biochemistry and purification protocols have been studied and developed by the participants of the ANR, iv) the proximity and easy access to the nearby world-class synchrotron and neutron small-angle scattering instruments (ESRF, ILL) will allow to record high-quality data sets that are needed for the project.

 

ANR Programme: JCJC - SVSE 5 - Physique, chimie du vivant et innovations biotechnologiques (JCJC SVSE 5) 2011

Project ID: ANR-11-JSV5-0003

Project coordinator:
Monsieur Frank Gabel (CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE - DELEGATION REGIONALE RHONE-ALPES SECTEUR ALPES)
frank.gabel@nullibs.fr

 

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The project coordinator is the author of this abstract and is therefore responsible for the content of the summary. The ANR disclaims all responsibility in connection with its content.