New Binding Mode of SLURP Protein to a7 Nicotinic Acetylcholine Receptor Revealed by Computer Simulations

Diankin, I.D.; Kudryavtsev, D.S.; Zalevsky, A.O.; Tsetlin, V.I.; Golovin, A.V.

Авторы: Diankin Igor D., Kudryavtsev Denis S., Zalevsky Arthur O., Tsetlin Victor I., Golovin Andrey V.
Журнал: Supercomputing Frontiers and Innovations
Том: 5
Номер: 4
Год издания: 2018
DOI: 10.14529/jsfi180407
Аннотация: SLURP-1 is a member of three-finger toxin-like proteins. Their characteristic feature is a set of three beta strands extruding from hydrophobic core stabilized by disulfide bonds. Each beta-strand carries a flexible loop, which is responsible for recognition. SLURP-1 was recently shown to act as an endogenous growth regulator of keratinocytes and tumor suppressor by reducing cell migration and invasion by antagonizing the pro-malignant effects of nicotine. This effect is achieved through allosteric interaction with alpha7 nicotinic acetylcholine receptors (alpha-7 nAChRs) in an antagonist-like manner. Moreover, this interaction is unaffected by several well-known agents specifically alpha-bungarotoxin. In this work, we carry out the conformational analysis of the SLURP-1 by a microsecond-long full-atom explicit solvent molecular dynamics simulations followed by clustering, to identify representative states. To achieve this timescale we employed a GPU-accelerated version of GROMACS modeling package. To avoid human bias in clustering we used a non-parametric clustering algorithm Affinity Propagation adapted for biomolecules and HPC environments. Then, we applied protein-protein molecular docking of the ten most massive clusters to alpha7-nAChRs in order to test if structural variability can affect binding. Docking simulations revealed the unusual binding mode of one of the minor SLURP-1 conformations.
Добавил в систему: Залевский Артур Олегович

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New Binding Mode of SLURP Protein to a7 Nicotinic Acetylcholine Receptor Revealed by Computer Simulationsстатья

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