Guidelines To Predict Binding Poses of Antibody-Integrin Complexes

ACS Omega
Beatriz ChavesJoão H M da Silva

Abstract

Integrins are cell adhesion receptors that transmit bidirectional signals across the plasma membrane. They are noncovalently linked heterodimeric molecules consisting of two subunits and act as biomarkers in several pathologies. Thus, according to the increase of therapeutic antibody production, some efforts have been applied to produce anti-integrin antibodies. Here, we purposed to evaluate methods of generation and identification of the binding pose of integrin-antibody complexes, through protein-protein docking and molecular dynamics simulations, and propose a strategy to assure the confidence of the final model and avoid false-positive poses. The results show that ClusPro and GRAMM-X were the best programs to generate the native pose of integrin-antibody complexes. Furthermore, we were able to recover and to ensure that the selected pose is the native one by using a simple rule. All complexes from ClusPro in which the first model had the lowest energy, at least 5% more negative than the second one, were correctly predicted. Therefore, our methodology seems to be efficient to avoid misranking of wrong poses for integrin-antibody complexes. In cases where the rule is inconclusive, we proposed the use of heated molecular dynam...Continue Reading

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Citations

Feb 10, 2021·Journal of Biomolecular Structure & Dynamics·Aline de Oliveira AlbuquerqueJoão Hermínio Martins da Silva

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Methods Mentioned

BETA
interaction prediction

Software Mentioned

DockScore
FireDock
Hex
DockQ
PatchDock
Cluspro
ZDOCK
HADDOCK
CAPRI
GRAMM

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