title: Binding of fullerenes and nanotubes to MscL.
abstract: Multi-drug resistance is becoming an increasing problem in the treatment of bacterial infections and diseases. The mechanosensitive channel of large conductance (MscL) is highly conserved among prokaryotes. Evidence suggests that a pharmacological agent that can affect the gating of, or block the current through, MscL has significant potential as a new class of antimicrobial compound capable of targeting a range of pathogenic bacteria with minimal side-effects to infected patients. Using molecular dynamics we examine the binding of fullerenes and nanotubes to MscL and demonstrate that both are stable within the MscL pore. We predict that fullerenes will attenuate the flow of ions through MscL by reducing the pore volume available to water and ions, but nanotubes will prevent pore closure resulting in a permanently open pore. Moreover, we confirm experimentally that it is possible to attenuate the flow of ions through MscL using a C60-γ cyclodextrin complex.
authors.affiliation: Computational Biophysics Group, Research School of Biology, Australian National University, ACT 0200, Australia.
authors.forename: Tamsyn A
authors.initials: TA
authors.lastname: Hilder
authors.affiliation: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, NSW 2010, Australia.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ridone
authors.affiliation: Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, NSW 2010, Australia.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: 1] Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, NSW 2010, Australia [2] St Vincent's Clinical School, The University of New South Wales, Victoria St, St Vincent's Hospital Darlinghurst NSW 2010, Australia.
authors.forename: Boris
authors.initials: B
authors.lastname: Martinac
authors.affiliation: Computational Biophysics Group, Research School of Biology, Australian National University, ACT 0200, Australia.
authors.forename: Shin-Ho
authors.initials: SH
authors.lastname: Chung
mesh_terms: D001665:Binding Sites; D001896:Boron Compounds / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry*; D037741:Fullerenes / Q000737:chemistry*; D007473:Ion Channels / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D037742:Nanotubes, Carbon / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D001896:Boron Compounds; D029968:Escherichia coli Proteins; D037741:Fullerenes; D007473:Ion Channels; C086596:MscL protein, E coli; D037742:Nanotubes, Carbon; C017282:boron nitride