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Poster

E(3)-equivariant models cannot learn chirality: Field-based molecular generation

Alexandru Dumitrescu · Dani Korpela · Markus Heinonen · Yogesh Verma · Valerii Iakovlev · Vikas Garg · Harri Lähdesmäki

Hall 3 + Hall 2B #9
[ ]
Fri 25 Apr midnight PDT — 2:30 a.m. PDT

Abstract:

Obtaining the desired effect of drugs is highly dependent on their molecular geometries. Thus, the current prevailing paradigm focuses on 3D point-cloud atom representations, utilizing graph neural network (GNN) parametrizations, with rotational symmetries baked in via E(3) invariant layers. We prove that such models must necessarily disregard chirality, a geometric property of the molecules that cannot be superimposed on their mirror image by rotation and translation. Chirality plays a key role in determining drug safety and potency. To address this glaring issue, we introduce a novel field-based representation, proposing reference rotations that replace rotational symmetry constraints. The proposed model captures all molecular geometries including chirality, while still achieving highly competitive performance with E(3)-based methods across standard benchmarking metrics.

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