E u r o S c i C o n c o n f e r e n c e o n
Protein, Proteomics and
Computational Biology
Biochemistry & Molecular Biology Journal
ISSN: 2471-8084
D e c e m b e r 0 6 - 0 7 , 2 0 1 8
Am s t e r d a m , N e t h e r l a n d s
Proteomics and Computational Biology 2018
Page 22
T
oday, soluble proteins are managed routinely within the project timelines
and scope with the rapid portfolio changes in pharmaceutical industry.
Establishment of biophysical and structure-based methods for transmembrane
proteins still represents a significant challenge to have an impact on drug
discovery. leadXpro combines membrane protein expression, purification and
structure determination coupled to premium access to the synchrotron Swiss
Light Source (SLS), the Free Electron Laser (SwissFEL) and single particle cryo-
electron microscopy (cryo-EM) at the University of Basel. LeadXpro also confronts
structural data to different biophysical measurements like thermal shift assays,
radiobinding assay and wave guide interferometry in order to generate better
lead molecules with appropriate features. The talk will show advancements in
projects and technologies with examples for serial crystallography performed
at synchrotron and free electron laser enabling structure determination of
challenging drug targets. Moreover, recent efforts and implementation of wave-
guide interferometry method for analysis of small (fragment-like molecules)/large
ligand binding kinetics on membrane proteins will be discussed in the context of i)
lead discovery and optimization ii) biologics targeting membrane proteins. Finally,
recent progress in cryo-EM will also be discussed.
Area of Interest:
• X-ray Crystallography
• Cryo-Electron Microscopy
• Biophysical methods & characterization (TSA & SPR)
• Membrane Proteins & Hot Structures
Biography
Nicolas studied at the University of Compiegne (France) and
completed his Engineer in Biotechnology degree. For his
master and PhD in Neuroscience from the University Pierre et
Marie Curie, hemoved to the Pasteur Institute in Paris, where he
worked in the group of Dr. Pierre-Jean Corringer and Prof. Jean-
Pierre Changeux (Channel receptors group) on the elucidation
of the crystal structure of a pentameric ligand gated ion channel
in an open conformation. From 2009 to 2013, Nicolas moved to
FMI (Friedrich Miescher Institute for Biomedical research) as a
post-doctoral fellow in the group of Dr. Nicolas Thomae, where
he worked on the mechanisms of Holliday junction dissolution
by solving the structure of the human Topoisomerase III in
complex with a modulatory protein called RMI1. From 2013 to
2017, he worked at Roche, first as a Roche post doctoral fellow
and after as a scientist in the Chemical biology department
developing biophysical methods for membrane proteins as well
as producing, purifying, stabilizing and characterizing GPCRs,
transporters and membrane enzymes. Starting February
2017, Nicolas will work on biophysical and structural biology
programs within LeadXpro AG as a senior scientist.
Nicolas.bocquet@leadxpro.comStructure based drug discovery on
membrane protein targets
Nicolas Bocquet, Sandra Markovic-Mueller,
Robert Cheng, Mathieu Botte, Wassim
AbdulRahman, Sophie Huber, Eric Pflichta,
Denis Bucher and Michael Hennig
leadXpro AG, PARK INNOVAARE, 5234 Villigen, Switzerland
Nicolas Bocquet et al., Biochem Mol biol J Volume:4
DOI: 10.21767/2471-8084-C5-020