Presented by
Dr. Alexander Grishaev
Alexander V Grishaev, PhD obtained his undergraduate degree in Chemistry with a specialization in Quantum Chemistry from Mosc Alexander V Grishaev, PhD obtained his undergraduate degree in Chemistry with a specialization in Quantum Chemistry from Moscow State University in 1993. He earned his PhD in Chemistry/Biophysics from Carnegie Mellon University in 2001, focusing on protein structure determination via solution NMR. His post-doctoral research was conducted at the National Institutes of Health (NIH), where he studied the structure of proteins and RNA using NMR and SAXS techniques. In 2005, Dr. Grishaev became a staff scientist at NIH, and in 2015, he transitioned to a Principal Investigator position at the National Institute of Standards and Technology (NIST). His primary research interests lie in determining protein and RNA structures through hybrid methods centered on SAXS, combining experimental and computational approaches, with a particular focus on conformational flexibility.
Organizer
Ana Tutueanu, PhD

Structure and Dynamics of Flexibly-Linked, Multi-Domain Proteins from Scattering, Spins, and Simulations

Webinar
29/10/2024
15:00

Antibody-based pharmaceuticals are the leading biologic drug platform (> $75B/year). Despite a wealth of information collected on them, there is still a lack of knowledge on their inter-domain structural distributions, which impedes both formulation optimization and understanding of their interactions with the binding partners. To address this measurement gap, we have developed a new methodology to derive biomolecular structure ensembles from small- and wide-angle scattering data supplemented by distance distribution measurements via a library of tagged proteins bound to an unlabeled and otherwise unmodified target biologic. We have employed the NIST monoclonal antibody (NISTmAb) reference material as our development platform towards a general and extendable technology compatible with any non-isotopically labeled immunoglobulin G class mAb. Integrating SAXS/WAXS data with molecular simulations with the DEER measurements, we enable simultaneous determination of structural distributions and dynamics of mAb-based biologics.

What you will learn:

01

How SAXS/WAXS techniques are advancing structural characterization of antibody-based biologics

02

The critical role of inter-domain structural distribution in therapeutic antibodies development

03

Novel methodologies which enable simultaneous determination of structural distributions and
dynamics of monoclonal antibodies based therapeutics

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