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EMBO course on biomolecular simulation 18-25 July 2004.

NOTE: the course is very much overbooked. We were forced to reject many good applications. All accepted participants have been notified directly by email.

Molecular simulation techniques have never been as accessible and as valuable to biologists as they are now. The function of biological macromolecules is determined by their three-dimensional structure and dynamics. Knowledge of the structure is necessary for understanding their mechanism. This is the driving force behind structural genomics projects, which can therefore be understood as part of functional genomics. In particular for structures from these large-scale efforts, interpretation is difficult since independent biological experimental knowledge may be unavailable. Modelling techniques help in identifying ligands and predicting the dynamics that is essential for the function of the molecule. X-ray/electron crystal or NMR structures themselves are only stills of the biologically active, dynamic molecules. Disregarding some rare exceptions, there is no experimental technique that can observe dynamics in atomic detail, and interpretation of spectroscopic characterizations of dynamics is another important application of molecular simulation. Even with structural genomics projects showing the first results, the structure-sequence gap is widening at an increasing speed. Modelling is therefore becoming a major source of structural information.

On the technical side, ever more powerful computers enable longer simulations and consequently more meaningful results, and greater scope for direct comparison with experiment. New experimental techniques (such as atomic force spectroscopy and optical tweezers for studying single molecules) create new needs for simulation. Further, advances in modelling and simulation methodology are bringing improved accuracy and possibilities for new applications.

Simulation techniques allow dynamic as well as structural features to be explored. They permit computation of thermodynamic and kinetic properties. They may be used to predict effects of mutations and changes in environmental conditions such as pH. They are valuable in the design and redesign of new molecules. Increasingly, therefore, non-specialists will find it necessary to apply simulation techniques to biological macromolecules. The software has become easier to obtain and often provides user-friendly graphical interfaces. It is however essential to understand the basic principles underlying different simulation techniques, and it is by no means easy for the novice user to understand how to use powerful software to greatest advantage, and results can be misinterpreted. The EMBO practical course will address three types of simulation: quantum mechanics, molecular mechanics/dynamics and Brownian dynamics. These permit simulation on different temporal and spatial scales. They may be used as follows:

Quantum mechanics combined with molecular mechanics (in QM/MM calculations) to investigate enzyme mechanisms and redox properties.

Molecular mechanics models with molecular dynamics or Monte Carlo simulations to refine macromolecular structures, simulate dynamic motions and compute thermodynamic and kinetic properties.

Brownian dynamics to simulate diffusional motion for molecular association and conformational transitions.

One aim will be to provide the basic theory and practical hints for such users e.g. biologists who want to simulate the molecule they are doing experiments on. Another type of student will be doing theoretical research in a related area e.g. homology modelling, or with one of the simulation techniques and wish to learn how to expand their calculations to use (other) simulation techniques.

At the end of the course, it is the intention that each student will have a reasonable grasp of the theory behind each simulation method and know how to put this into practice. Exercises will be done with software of minimal cost so that users can continue once they get home. Assistance will be provided with application of the methods to the students' own projects.

Tentative program

The course will start on Sunday 18th of July around 15h00 and finish on Saturday 24th of July with dinner.

Force fields
Molecular mechanics: energy minimization
Molecular dynamics
Monte Carlo techniques
Essential dynamics/ normal modes
Free energies
Brownian dynamics
Combining quantum mechanics and molecular mechanics approaches
Programming techniques
Molecular graphics
Modelling: some basics of mutations/sequence analysis
Docking/ drug design

Practicals will cover application of these techniques to enzyme mechanism, protein and peptide folding, DNA/RNA binding and carbohydrate conformational characterization.

Speakers and instructors:

Rebecca Wade, EML Heidelberg
Tom Simonson, Ecole Polytechnique, Palaiseau
Richard Lavery, IBPC, Paris
Konrad Hinsen, Centre de Biophysique Moleculaire, Orleans
Anna Tramontano, University of Rome
Warren DeLano, DeLano Scientific, San Francisco
David Case, Scripps Institute, La Jolla
Martin Field, IBS, Grenoble
Paolo Carloni, International School for Advanced Studies, Trieste
Michael Nilges, Pak-Lee Chau, Tru Huynh, Arnaud Blondel, Rachid Maroun, Institut Pasteur, Paris

Course fees and registration

NOTE: the course is very much overbooked. We were forced to reject many good applications. All accepted participants have been notified directly by email.

Please send an application by email (ascii preferred) to Michael Nilges, containing the following information:
(1) a short CV, with a list of publications (if possible);
(2) a letter of motivation indicating how the course will help you in your research;
(3) an abstract for a poster.
For participants from academic institutions, there are no course fees. All local expenses are paid by EMBO. Travel has to be paid by the participants.

The deadline for applications was 15th of May, 2004.

For more information, contact Michael Nilges or Rebecca Wade

NOTE: the course is very much overbooked. We were forced to reject many good applications. All accepted participants have been notified directly by email.

Course Materiel

Some course materiel is available:
Tom Simonson: Electrostatics
Konrad Hinsen: Normal modes
Konrad Hinsen: Programming

author: Michael Nilges
last change: June 1, 2004