The 2014 Lectures in Chemistry and Biology: Molecular Conformational Fluctuations: Origins of Biological Specificity and Applications in Pharmacochemistry

Francis Crick once said: "When you do not understand function, study structure". The crystallographers, followed this advice and gave us a large repertoire of protein and nucleic acid structures. In some cases, this linkage was obvious but not for all.

When Kurt Wutrhich introduced Nuclear Magnetic Resonance spectroscopy (NMR) to the study of proteins a whole new appreciation of the structure/function linkage became apparent. The reason is easily understood: Crystallography captures the structure of the molecular conformation which yields the best crystal lattice and where the molecules have extremely low mobility and flexibility; essentially behaving as rigid bodies. In contrast, NMR reveals how macromolecules behave in solution; it captures molecular dynamics. And certain conformational states within the range of this dynamic ensemble are coupled to specific functions.

The regulation of all cellular activities is achieved through the action of specialized molecules, mostly proteins (and some RNAs). Both of these are, in physical and chemical terms, large multiatomic ensembles bonded together in some specific sequence of subunits (amino acids or nucleotides). The functional properties of each of these ensembles are manifested only when each of them folds into a unique 3-D structure (fold), sometimes with several thermodynamic sub-domains. Recent evidence is telling us that even this 3-D structure is an average among a multitude of conformational states, all in rapid and reversible equilibrium. Sometimes, the population of these sub-states is driven to a completely different fold. Macromolecules in solution "dance" and these dances are influenced by the properties of their microscopic environment, i.e., the composition of the solvent in which they "swim", just as Chris Anfinsen had predicted many years earlier: the essential linkage between amino acid sequence and environment to yield a unique functional structure.

This year our Lecture Series will focus on the basic methodologies for capturing the conformational fluctuations of macromolecules as they relate to protein stability, folding and function. Furthermore, we will examine the thermodynamics of these fluctuations and the selectivity and specificity of interactions between macromolecules and with the ligands that affect them. The latter will be linked to specific examples of cellular regulation (allostery, transcription, translation, transport, etc) and with the design and optimization of novel pharmaceuticals (intelligent drug design) that can modulate these conformational fluctuations. It is the hope that at the end, the students would be able to better appreciate that molecular selectivity and specificity are emerging properties of the system and their emergence can be manipulated and controlled to achieve tangible benefits.

Kurt Wüthrich
Professor, ETH, Zurich, Switzerland and
The Scripps Research Institute, La Jolla, CA, USA.
Nobel Prize (2002) in Chemistry

Ernesto Freire
Professor, Department of Biology, Johns Hopkins University, Baltimore, USA

Vincent Hilser
Professor and Chair, Department of Biology, Johns Hopkins University, Baltimore, USA

Birthe B. Kragelund
Professor, Structural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Hartmut Oschkinat
Professor, Leibniz Institut fur Moleculare Pharmakologie, Berlin, Germany.

Hans W. Spiess
Professor, Max Planck Institute for Polymer Research, Mainz, Germany

Gerhard Wagner
Professor, Harvard Medical School, Boston, USA
Monday 25 August 09:00 - 09:45R e g i s t r a t i o n
09:45 - 10:00Welcome
10:00 - 11:15"Exploring the Protein Universe with Tools of Structural Biology"
Prof. Kurt Wüthrich
11:15 - 11:45B r e a k
11:45 - 13:00"Protein Dynamic seen with NMR in Solution"
Prof. Kurt Wüthrich
13:00 - 14:30L u n c h   B r e a k
14:30 - 15:45"Conformational Fluctuations and Intrinsic Protein Disorder in Signaling",
Prof. Vincent Hilser
Tuesday 26 August09:30 - 10:45"Thermodynamic Based Approach to Drug Design"
Prof. Ernesto Freire
10:45-11:15B r e a k
11:15 - 12:30"Development of Inhibitors of HIV-1 Cell Infection"
Prof. Ernesto Freire
12:30 - 14:00L u n c h  B r e a k
14:00 - 15:15"Advanced magnetic resonance techniques for elucidating structure and dynamics of nanostructured organic functional systems", PART I.
Prof. Hans W. Spiess
Wednesday 27 August09:30 - 10:45"Advanced magnetic resonance techniques for elucidating structure and dynamics of nanostructured organic functional systems", PART II.
Prof. Hans W. Spiess
10:45 - 11:15B r e a k
11:15 - 12:30"Probing for Local Unfolding in Conformational Fluctuations of Enzymes",
Prof. Vincent Hilser
12:30 - 14:00L u n c h   B r e a k
20:00 "Our Proteins and Daily Life"
Public Lecture by Prof. Kurt Wüthrich
Thursday 28 August09:30 - 10:45"Dynamic Nuclear Polarisation for Studying Molecular Machines"
Prof. Hartmut Oschkinat
10:45 - 11:15B r e a k
11:15 - 12:30"Chaperone Systems Studied by NMR"
Prof. Hartmut Oschkinat
12:30 - 14:00L u n c h   B r e a k
14:00 - 15:15"Dynamic interactions of translation factors regulated by tumor suppressors and allosteric inhibitors"
Prof. Gerhard Wagner
Friday 29 August09:30 - 10:45"Protein interactions regulating T - cell activation and sterol synthesis"
Prof. Gerhard Wagner
10:45 - 11:15B r e a k
11:15 - 12:30"Functional dynamics and its importance for cytokine receptor antagonist development"
Prof. Birthe B. Kragelund
12:30 - 14:00L u n c h   B r e a k
14:00 - 15:15"Intrinsic disorder in membrane proteins"
Prof. Birthe B. Kragelund
15:15 - 15:30Closing Remarks by Prof. Van Moudrianakis

NEW Deadline for Application
Thursday July 31, 2014



Researchers, Postdoctoral Associates, Graduate
and advanced Undergraduate students.

Financial Aid


The Onassis Foundation will support travel and accommodation expenses for up to thirty five Greek students and up to fifteen International students, selected on the basis of their academic performance. The financial aid for the travel of non-European students cannot exceed the maximum amount of the reimbursement provided for the travel of European students. Interested students should attach to their CV, a list of courses taken, their grades and two letters of recommendation. Excellent knowledge of English is required.



Students admitted on the basis of their academic performance will receive a certificate after successful participation in the lectures.


Application Form*
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Dear Sir,
I wish to participate in "The 2014 Lectures in Chemistry and Biology"

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Please attach your CV (if applicable): (Select your CV file from your computer).

Additional Requirements for Students

  • Graduate students should attach their CV with a detailed description of their studies so far. Advanced undergraduate students should add to their CV a list of courses taken and their grades.
  • Two letters of recommendation should be sent by E-mail directly by the recommending persons to: