State-of-the-art docking software produced a set of LDLR-HNP1 complex 3D models. Creation of a 3D motif capturing atomic interactions of the LDLR binding interface allowed selection of the most plausible configurations. Eventually, only two models were in agreement with the literature.
Binding energy estimations revealed that only one of them is particularly stable, but also interaction with LDLR weakens significantly bonds within the HNP1 dimer. This may be significant since it suggests a mechanism for internalisation of HNP1 in mammalian cells.
In addition to a novel approach for complex structure prediction, this study proposes a 3D model of the LDLR-HNP1 complex which highlights the key residues which are involved in the interactions. The putative identification of the receptor binding mechanism should inform the future design of synthetic HNPs to afford maximum internalisation, which could lead to novel anti-infective drugs.