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Molecular simulation - based analysis of signal transduction system in neuronal cells

Research Project

Project/Area Number 16500245
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTeikyo University

Principal Investigator

NISHIZAWA Kazuhisa  Teikyo University, School of Medicine, Associate Professor, 医学部, 助教授 (00260935)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥3,200,000 (Direct Cost: ¥3,200,000)
KeywordsMolecular dynamics / computational chemistry / シミュレーション / Kチャンネル
Research Abstract

Our initial goal was molecular dynamics simulation-based study of dynamics of the molecules interacting with PIP2 in presynaptic termini. While we confirmed that molecular orbital calculation and molecular simulations with Gromacs and NAMD packages work on our system, strong interaction due to phosphate groups of PIP2 made the time required for equilibration too long for simulaiton study. 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, using two different force … More fields, Gromacs and Charmm. The system reproduced the surface binding mode of HaTx1, in which HaTx1 resided in the extracellular-side (outer) 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. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (4 results)

All 2006 2005 Other

All Journal Article (4 results)

  • [Journal Article] Interaction between k^+ channel gate modifier hanatoxin and lipid bilayer membranes analyzed by mclecular dynamics simmkitin.2006

    • Author(s)
      Manami Nishizawa
    • Journal Title

      Eur. Biophys. J in press

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Interaction between K(+) channel gate modifier hanatoxin and lipid bilayer-membranes analysed by molecular dynamics simulation2006

    • Author(s)
      Manami Nishizawa
    • Journal Title

      Eur.Biophys.J (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] On slippage-like mutation dynamics within genes : a study of pseudogenes and 3'UTRs2005

    • Author(s)
      Manami nishizawa, Kazuhisa Nishizawa
    • Journal Title

      Journal of Molecular Evolution 60

      Pages: 274-275

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Interaction between K^+ channel gate modifier hanatoxin and lipid bilayer membranes analysed by molecular dynamics simulation

    • Author(s)
      Manami Nishizawa
    • Journal Title

      Eur.Biophys.J (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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