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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.com

Structure 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