Drug development using information from Neutron protein crystallography

Schrader, Tobias Erich; Ostermann, Andreas; Jüttner; Richter, Dieter; Petry; Monkenbusch, Michael; Laatsch, Bernhard; Longo, Marialucia

Conference Presentation (After Call)

FZJ-2018-03724

Drug development using information from Neutron protein crystallography

Schrader, T. E. (Corresponding author)FZJ* ; Ostermann, A.MLZ* ; Longo, M.FZJ* ; Monkenbusch, M.FZJ* ; Laatsch, B.FZJ* ; Jüttner ; PetryMLZ* ; Richter, D.FZJ*

2017

Neutrons for Health Conference, Bad Reichenhall, Germany, 27 Jun 2017 - 30 Jun 2017

Please use a persistent id in citations: http://hdl.handle.net/2128/19204

Abstract: Neutron protein crystallography is a technique which can readily report on the hydrogen atom positions in proteins. This is in some cases valuable information on drug target proteins and their hydrogen bonding with substrates and inhibitors. Other main scientific questions addressed are: protonation states of amino acids in intermediate states of the catalytic process and determining the correct structure of metallo-proteins which are subjected to reduction due to the radiation damage caused by x-rays. As an example for a neutron diffractometer, the instrument BIODIFF is introduced: It is a joint project of the Jülich Centre for Neutron Science (JCNS) and the FRM II. BIODIFF is designed as a monochromatic instrument with a narrow wavelength spread of less than 3 %. To cover a large solid angle the main detector of BIODIFF consists of a neutron imaging plate in a cylindrical geometry with online read-out capability. The main advantage of BIODIFF is the possibility to adapt the wavelength to the size of the unit cell of the sample crystal while operating with a clean monochromatic beam that keeps the background level low.In this contribution, a review of most recent application examples of neutron protein crystallography for drug development is given. Especially the need for large protein crystals (typically > 0.5 mm3 in volume) is addressed.

Keyword(s): Health and Life (1st) ; Biology (2nd)

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