Oxford University, Structural Bioinformatics & Computational Biochemistry Unit

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Dr. Phillip J. Stansfeld

Structural Bioinformatics and Computational Biochemistry Unit Department of Biochemistry University of Oxford South Parks Road Oxford OX1 3QU Telephone: +44 1865 613304 Fax: +44 1865 613238 Email:


Research

	Inward Rectifier Potassium Channels - Homology Modelling & Molecular Dynamics Simulations Potassium (K) channels are intrinsic membrane proteins that control the selective permeation of K ions. The three-dimensional architecture of these channels has been revealed by the determination of crystal structures of a number of K channel proteins. The resolved coordinates may be used to create homology models of other members of the Potassium channel family. Atomistic and coarse-grained molecular dynamics simulations can then be utilised to enable further characterisation of both the crystal and homology modelled structures; with attention focussed on pore gating, K coordination and protein-membrane interactions. The inward rectifier K channel, Kir6.2, is the primary K channel of interest. This work is in collaboration with Professor Frances Ashcroft in the Department of Physiology, Anatomy & Genetics.

Publications
Piechotta PL, Rapedius M, Stansfeld PJ, Bollepalli MK, Erhlich G, Andres-Enguix I, Fritzenschaft H, Decher N, Sansom MS, Tucker SJ, Baukrowitz T. (2011) EMBO J The pore structure and gating mechanism of K2P channels. Mannikko R, Stansfeld PJ, Ashcroft AS, Hattersley AT, Sansom MSP, Ellarn S, Ashcroft FM (2011) J Physiol A Conserved Tryptophan at the Membrane-Water Interface Acts as a Gatekeeper for Kir6.2/SUR1 Channels and Causes Neonatal Diabetes when Mutated. Stansfeld PJ, Sansom MSP (2011) JCTC From Coarse Grained to Atomistic: A Serial Multiscale Approach to Membrane Protein Simulations Streit AK, Netter MF, Kempf F, Walecki M, Rinne S, Bollepalli MK, Preisig-Muller R, Renigunta V, Daut J, Baukrowitz T, Sansom MSP, Stansfeld PJ, Decher N. (2011) JBC A specific two-pore-domain potassium channel blocker defines the structure of the task-1 open pore. Muskett FW, Thouta S, Thomson SJ, Bowen A, Stansfeld PJ, Mitcheson JM (2010) JBC Mechanistic insight into hERG K+ channel deactivation gating from the solution structure of the EAG domain. Domanski J, Stansfeld PJ, Sansom MS, Beckstein O (2010) J Membr Biol Lipidbook: a public repository for force-field parameters used in membrane simulations. Stansfeld PJ, Hopkinson RJ, Ashcroft FM, Sansom MSP (2009) Biochemistry The PIP2 Binding Site in Kir Channels: Definition by Multi-scale Biomolecular Simulations. Ashmole I, Vavoulis DV, Stansfeld PJ, Mehta PR, Feng J, Sutcliffe MJ, Stanfield PR (2009) J Physiol The response of the tandem pore potassium channel TASK-3 (K2P9.1) to voltage: gating at the cytoplasmic mouth. Rouse SL, Carpenter T, Stansfeld PJ, Sansom MSP (2009) Biochemistry Simulations of the BM2 Proton Channel Transmembrane Domain from Influenza Virus B. Tai K, Stansfeld PJ, Sansom MSP (2009) Biochemistry Ion-Blocking Sites of the Kir2.1 Channel Revealed by Multiscale Modeling Tai K, Fowler P, Mokrab Y, Stansfeld P, Sansom MS (2009) Methods Cell Biol. Molecular Modeling and Simulation Studies of Ion Channel Structures, Dynamics and Mechanisms. Stansfeld PJ, Grottesi A, Sands ZA, Sansom MSP, Gedeck P, Gosling M, Cox B, Stanfield PR, Mitcheson JS, Sutcliffe MJ (2008) Biochemistry Insight into the Mechanism of Inactivation and pH Sensitivity in Potassium Channels from Molecular Dynamics Simulations. Hardman RM, Stansfeld PJ, Dalibalta S, Sutcliffe MJ, Mitcheson JS (2007) J. Bio. Chem. Activation gating of hERG potassium channels: S6 glycines are not required as gating hinges. Yuill KH, Stansfeld PJ, Ashmole I, Sutcliffe MJ, Stanfield PR (2007) Pflugers Arch. The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1: contributions of the pore domains. Stansfeld PJ, Gedeck P, Gosling M, Cox B, Mitcheson JS, Sutcliffe MJ (2007) Proteins. Drug block of the hERG potassium channel: Insight from modeling. Stansfeld PJ, Sutcliffe MJ, Mitcheson JS (2006) Expert Opin. Drug Metab. Toxicol. Molecular mechanisms for drug interactions with hERG that cause long QT syndrome. Perry M, Stansfeld PJ, Leaney J, Wood C, de Groot MJ, Leishman D, Sutcliffe MJ, Mitcheson JS (2006) Mol. Pharmacol. Drug binding interactions in the inner cavity of HERG channels: molecular insights from structure-activity relationships of clofilium and ibutilide analogs. Mitcheson J, Perry M, Stansfeld P, Sanguinetti MC, Witchel H, Hancox J (2005) Novartis Found. Symp. Structural determinants for high-affinity block of hERG potassium channels. Chen PE, Geballe MT, Stansfeld PJ*, Johnston AR, Yuan H, Jacob AL, Snyder JP, Traynelis SF, Wyllie DJ (2005) Mol. Pharmacol. Structural features of the glutamate binding site in recombinant NR1/NR2A N-methyl-D-aspartate receptors determined by site-directed mutagenesis and molecular modeling. Joint first author

Last updated 13th May 2011