1 Structure prediction of LDLR-HNP1 complex based on docking enhanced by LDLR binding 3D motif Reyhaneh Esmaielbeiki 1* , Declan P. Naughton 1 and Jean-Christophe Nebel 1 . 1 Faculty of Science, Engineering and Computing, Kingston University, Kingston-upon-Thames, KT1 2EE, UK *Correspondence to: Reyhaneh Esmaielbeiki, Faculty of Science, Engineering and Computing, Kingston University, Kingston-upon-Thames, KT1 2EE, UK. T: +44 (0)20 8417 7159. F:+44 (0)20 8417 2972. E-mail: R.Esmaielbeiki@kingston.ac.uk . Date of initial submission: 14-07-2011 Date of revised submission: - Date of final acceptance: 26-08-2011 ABSTRACT Human antimicrobial peptides (AMPs), including defensins, have come under intense scrutiny owing to their key multiple roles as antimicrobial agents. Not only do they display direct action on microbes, but also recently they have shown to interact with the immune system to increase antimicrobial activity. Unfortunately, since mechanisms involved in the binding of AMPs to mammalian cells are largely unknown, their potential as novel anti-infective agents cannot be exploited yet. Following the reported interaction of Human Neutrophil Peptide 1 dimer (HNP1) with a low density lipoprotein receptor (LDLR), a computational study was conducted to discover their putative mode of interaction. State-of-the-art docking software produced a set of LDLR-HNP1 complex 3D models. Creation of a 3D motif capturing atomic interactions of 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 not 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.