NONMEM Users Network Archive

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Webinar on Complex Drug-Protein Interactions

From: Rebecca Baillie <rbaillie>
Date: Tue, 12 Jan 2021 20:38:00 +0000

Building Kinetic Models with Complex Drug-Protein Interactions: application=
 to the targeted inhibition of MAPK signaling in cancer
Luca Gerosa, PhD, Postdoctoral Fellow, Laboratory of Systems Pharmacology, =
Harvard Medical School
Wednesday January 20, 2021, 12:00 to 1:00 pm EDT
Register at https://www.rosaandco.com/webinars
Abstract:
A key goal in the field of Quantitative Systems Pharmacology (QSP) is the c=
onstruction of mechanistic models able to predict drug efficacy. A major ch=
allenge in building such models is the necessity to properly describe highl=
y cooperative drug-protein and protein-protein interactions that govern the=
 functioning of biochemical networks. In this seminar, I will show how Ordi=
nary Differential Equations (ODEs) models comprising large numbers of drug-=
protein and protein-protein interactions can be efficiently built using rul=
e-based modelling and energy-based descriptions of molecular cooperativity.
The modelling framework I will present is based on an extension of the Pyth=
on Systems Biology (PySB) toolbox to incorporate energy-based specification=
s supported by BioNetGen (eBNG). The resulting framework allows modelers to=
 write large ODEs models as compact Python programs in which molecular coop=
erativity is specified as free energy contributions and detailed balance is=
 satisfied by construction. As a case study, I will show that the framework=
 allows the accurate description of high-order cooperativity interactions b=
etween components of the MAPK signaling pathway and targeted kinase inhibit=
ors and that the inclusion of such interactions predicts clinically-relevan=
t drug resistance mechanisms in skin and colorectal cancers.


Received on Tue Jan 12 2021 - 15:38:00 EST

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