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2020-12-02 - Colloque/Présentation - poster - Anglais - page(s)

Tonneaux Corentin , Uvyn Annemiek, Fossepre Mathieu , De Geest Bruno, Surin Mathieu , "Molecular modeling of multivalent antibody-recruiting molecules and their complexation by an antibody" in BioExcel Winter School, 2020

  • Codes CREF : Chimie théorique (DI1311)
  • Unités de recherche UMONS : Chimie des matériaux nouveaux (S817)
  • Instituts UMONS : Institut de Recherche en Science et Ingénierie des Matériaux (Matériaux), Institut des Biosciences (Biosciences)
  • Centres UMONS : Centre d’Innovation et de Recherche en Matériaux Polymères (CIRMAP)

Abstract(s) :

(Anglais) Immunotherapy is a type of treatment which uses the patient’s immune system to fight diseases such as cancer. Antibody-recruiting molecules (ARMs) constitute a promising class of molecular scaffolds in this field. These combine anchoring groups that target the surface of the cancer cells and haptens that bind endogenous antibodies, which are present in the serum, to trigger immune-mediated killing of target cancer cells. Multivalent ARMs, i.e. molecules that contain multiple haptens, revealed a better binding avidity towards the antibody in comparison to monovalent ARMs, and therefore may improve their therapeutic effect. In this work, we carry out molecular modelling simulations in order to get insights into the conformations and dynamics of specific ARMs, as well as their interactions with antibodies. Those simulations are performed with the GAFF2 forcefield in a water box model. Notably, we study the effect of the number of functional groups, their spacing, and the nature of the linkers on the conformation of ARMs as well as on their complexation to anti-DNP antibodies. The knowledge on the conformations and binding modes is fundamental to adapt the design of ARMs, to assess its binding to the antibody and thus improve its therapeutic effect. In particular, our results highlight the molecular parameters necessary to avoid the undesired interaction in between haptens on a single ARM.