Interaction between K+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by molecular dynamics simulation


DOI: 10.1007/s00249-006-0044-z

Cite this article as:
Nishizawa, M. & Nishizawa, K. Eur Biophys J (2006) 35: 373. doi:10.1007/s00249-006-0044-z


Hanatoxin (HaTx) is an ellipsoidal-shaped peptide that binds to the voltage sensor of voltage-dependent channels. Of physicochemical interest, HaTx has a “ring” of charged residues around its periphery and a hydrophobic protrusion. It has previously been postulated that HaTx binds to and functions on the surface of membranes, but a recent fluorescent-quenching study has implied a fairly deep positioning of HaTx in the lipid bilayer membrane. We carried out numerous molecular dynamic simulations of HaTx1, a well-studied variant of HaTx, in fully hydrated phospholipid bilayers. The system reproduced the surface-binding mode of HaTx1, in which HaTx1 resided in the extracellular side (outer) of the water/membrane interface with the hydrophobic patch of HaTx1 facing the membrane interior. On the other hand, analyses with various parameter settings suggested that the surface-binding mode was unstable because of the substantial attractive electrostatic force between HaTx1 and the lipid head groups of the inner (opposite) leaflet. Compared with this electrostatic force, the energetic cost for membrane deformation involving meniscus formation appeared to be small. In an attempt to interpret the quenching data, we consider the possibility of dimpling (meniscus formation) that brings HaTx1 inward (only ~0.7–0.8 nm above the bilayer center), while accounting for the flexibility of both leaflets of the membrane and the long-range interaction between positively charged residues of the membrane-bound peptide and the polar head groups of the opposite leaflet of the membrane. It is suggested that molecular dynamics simulations taking into account the flexibility of the membrane surface is potentially useful in interpreting the fluorescence-quenching data.


Molecular dynamics simulation Lipid–protein interactions Structural modelling 

Supplementary material

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Copyright information

© EBSA 2006

Authors and Affiliations

  1. 1.Department of BiochemistryTeikyo University School of MedicineTokyoJapan

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