structural-biology-2018-posters-accepted-abstracts

Structural Biology 2018

Volume: 4

Biochemistry & Molecular Biology Journal

Page 75

March 15-16 2018

Barcelona, Spain

Edition of International Conference on

Structural Biology

pplication of biophysical and structure-based methods in

membrane protein drug discovery projects still represents a

significant challenge. leadXpro combines expertise in membrane

protein expression, purification, structure determination and

application of biophysical methods to facilitate structure-based

design of novel medicines. The company has premium access

to the synchrotron (Swiss Light Source, SLS), the free electron

laser (SwissFEL) and single particle cryo-electron microscopy

(University of Basel). Serial femtosecond crystallography (SFX)

using X-ray free electron laser (XFEL) significantly increases

possibilities of obtaining structural information on membrane

proteins. SFX shows a number of advantages for structure-based

drug discovery: 1. the ability to determine structures from poor

quality crystals shortens the timelines for structure determination

and makes some drug targets, such as challenging membrane

proteins accessible; 2. higher resolution improves the accuracy

of structure determination and interpretation of electron density

(morereliableplacementofligandatoms);3.structuralinformation

at room temperature (alone or in addition to cryo structures) gives

better insight into protein and ligand conformational dynamics; 4.

structures of proteins or ligands with radiation-sensitive groups

benefit from minimal radiation damage; 5. the most exciting

opportunity of FELs lies with time-resolved analysis of ligand

binding and associated protein conformational change. All the

benefits will have an impact on the discovery of lead compounds

for G-protein coupled receptors, ion channels and transporters.

Serial crystallography: opportunity for structure-based

drug discovery on membrane proteins

Sandra Markovic-Mueller

leadXpro AG, Switzerland

Biochem Mol biol J, Volume 4

DOI: 10.21767/2471-8084-C1-009