Dr. Philip W. Fowler


Structural Bioinformatics and Computational Biochemistry Unit
Department of Biochemistry
University of Oxford
South Parks Road
Oxford
OX1 3QU
U.K.

Telephone: +44 1865 613304
Fax: +44 1865 613238

e-mail:
Portrait of Dr. Fowler
division line


Publication statistics

My H-index is 15. For the current value please see my Google Scholar or WoK pages. Alternatively visit my ImpactStory page. My list of publications is at the base of this page. I am also a Mendeley advisor and have a Mendeley profile.


Research Interests

I have worked in a large number of interesting areas. My current areas of research are summarised below. The references refer to my list of publications.


Cell signalling

I am studying the localisation of Ras proteins to different lipid bilayers and what modulates their binding. This is a difficult non-equilibrium process and spans a large range of length and time-scales


Ion channels

Ion channels are exquisitely-sensitive protein machines which selectively conduct ions at often high rates and are able to open and close their pores in response to a wide range of stimuli. Molecular simulation is a vital way of improving our understanding of these subtle proteins. I have studied the selectivity of K channels [11] and am working with Stephen Tucker and Thomas Baukrowitz on Kir1.1. [9,10,13,14,16]


Peptide transporters

hPepT1 is a member of the SLC15 family and transports di- and tri-peptides across the lining of the gut and is one of the main routes how we absorb dietary nitrogen. They also transport a wide range of drugs including some beta-lactam antibiotics, valacyclovir and L-Dope-Phe. I am working with Simon Newstead to understand how bacterial homologues transport di- and tri-peptides [17, 18] with the ultimate aim of developing a computational process that can predict chemical modifications to drug scaffolds that improve their bioavailability, by increasing their transport by hPepT1.


e-Infrastructure and grid computing

I have had a long interest in developing novel methods for accelerating calculations using grid computing [2,3,5,8]. I am also a Co-Investigator on the EPSRC SeIUCCR project whose aim is to encourage the use of e-Infrastructure within the UK academic community.


Blog

I keep a blog - please see this page.


Teaching

I lecture the first-year biochemists on non-covalent interactions and protein-folding and have run a workshop on ABC transporters for the fourth years. I give revision mathematics tutorials to the first-years when required. I am keen to try innovative ways of teaching and have used Mendeley to encourage undergraduates to read the primary literature. I am also arranging the first Software Carpentry workshop in Oxford to help researchers improve their core computational skills - please see my blog posts.


Publications

If you would like to read a paper please click on the DOI link to go to the journal's page, or go to my Mendeley profile where you can get PDFs.

* joint first author, ^ joint corresponding author

31. Fowler PW, Helie J, Duncan AM,Chavent M, Koldsoe H, Sansom MSP. Membrane stiffness is modified by integral membrane proteins. Under review

30. Samsudin F, Parker JL, Sansom MSP, Newstead S and Fowler PW Accurate Prediction of Ligand Affinities for a Proton-Dependent Oligopeptide Transporter. (2016) Cell Chem. Biol. doi:10.1016/j.chembiol.2015.11.015

29. Beale JH, Parker JL, Samsudin F, Barret AL, Senan A, Bird LE, Scott D, Owens RJ, Sansom MSP, Tucker SJ, Meredith D, Fowler PW, and Newstead S. Crystal structures of the extracellular domain from PepT1 and PepT2 provide novel insights into mammalian peptide transport. Structure. 23 1889-1899 doi:10.1016/j.str.2015.07.016

28. Jefferys E, Sands ZA, Shi J, Sansom MSP, Fowler PW Alchembed : A computational method for incorporating multiple proteins into complex lipid geometries. (2015) J Chem Theo Comp. 11 2743-2743 doi:10.1021/ct501111d

27. Reddy T, Shorthouse D, Parton D, Jefferys E, Fowler PW, Chavent M, Baaden M, Sansom MSP. Nothing to sneeze at: a dynamics and integrative computational model of an influenza virion. (2015) Structure. 23 584-597 doi:10.1016/j.str.2014.12.019

26. Fowler PW*^, Orwick-Rydmark M*, Radestock S*, Solcan N*, Dijkman P, Lyons JA, Kwok J, Caffrey M, Watts A, Forrest LR^ and Newstead S^. Gating topology of the proton coupled oligopeptide symporters. (2015) Structure 23 290-301 doi:10.1016/j.str.2014.12.012

25. Fowler PW*, Bollepalli MK*, Rapedius M, Shang L, Nematian E, Sansom MSP, Tucker SJ, Baukrowitz T. Insights into the structural nature of the transition state in the Kir channel gating pathway. (2014) Channels. 8 551-554 doi:10.4161/19336950.2014.962371

24. Bollepalli MK*, Fowler PW*, Rapedius M, Shang L, Sansom MSP, Tucker SJ, Baukrowitz T. State-Dependent Network Connectivity Determines Gating in a K+ Channel. (2014) Structure. 22 1037-1046 doi:10.1016/j.str.2014.04.018

23. Jefferys E, Sansom MSP, Fowler PW^ Visualising large three-component lipid bilayers that phase separate and undulate. (2014) RSC Faraday Discussion 169 209-223 doi:10.1039/c3fd00131h

22. Stelzl L, Fowler PW, Sansom MSP and Beckstein O. Flexible gates generate occluded intermediates in the transport cycle of LacY. (2014) J. Mol. Biol. 426 735-751 doi:10.1016/j.jmb.2013.10.024

21. Fowler PW, Abad E, Beckstein O and Sansom MSP. Energetics of multi-ion conduction pathways in potassium ion channels. (2013) J. Chem. Theo. Comput. 9 5176-5189 doi:10.1021/ct4005933

20. Fowler PW, Beckstein O, Abad E and Sansom MSP. Detailed examination of a single conduction event in a potassium channel. (2013) J Phys Chem Lett. 4 3104-3109 doi:10.1021/jz4014079

19. Fowler PW^ and Samson MSP^ The pore of voltage-gated potassium ion channels is strained when closed. (2013) Nature Communications 4 1872 doi:10.1038/ncomms2858

18. Solcan N, Kwok J, Fowler PW, Cameron AD, Drew D, Iwata S and Newstead S Alternating access mechanism in the POT family of oligopeptide transporters (2012) EMBO J. 31 3411-3421 doi:10.1038/emboj.2012.157

17. Newstead S, Drew D, Cameron AD, Postis VLG, Xiobing X, Fowler PW, Ingram, JC, Carpenter EP, Sansom MSP, McPherson MJ, Baldwin SA and Iwata S Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters PepT1 and PepT2 (2011) EMBO J. 310 417-426 doi:10.1038/emboj.2010.309

16. Paynter JJ, Andres-Enguix I, Fowler PW, Tottey S, Cheng W, Enkvetchakul D, Bavro VN, Kusakabe Y, Sansom MSP, Robinson NJ, Nichols CG and Tucker SJ Functional complementation and genetic deletion studies of KirBac channels: activatory mutations highlight gating-sensitive domains (2010) J Biol Chem. 285 40754-40761 doi:10.1074/jbc.M110.175687

15. Newstead S*, Fowler PW*, Bilton P*, Carpenter E, Sadler PJ, Campopiano DJ, Sansom MSP and Iwata S Insights into how nucleotide-binding domains power ABC transport (2009) Structure 17 1213-1222 doi:10.1016/j.str.2009.07.009

14. Abad E, Reingruber J, Fowler PW and Sansom MSP A Novel Rate Theory Approach to Transport in Ion Channels (2008) In AIP Conference Proceedings, Volume 1102 (Theory and Applications of Computational Chemistry), pages 236-243 doi:10.1063/1.3108380

13. Tai K, Fowler PW, Mokrab Y, Stansfeld PJ and Sansom MSP Molecular Modeling and Simulation Studies of Ion Channel Structures, Dynamics and Mechanisms (2008) Chapter 12 in Methods in Cell Nano Biology Volume 90 (edited by Bhanu P. Jena). 233-265

12. Psachoulia E, Fowler PW, Bond PJ and Sansom MSP Helix-Helix interactions in membrane proteins: Coarse grained simulations of Glycophorin helix dimerization (2008) Biochemistry. 47 10503-10512 doi:10.1021/bi800678t

11. Fowler PW, Tai K and Sansom MSP. The selectivity of K+ ion channels: testing the hypotheses (2008) Biophys. J. 95 5062-5072 doi:10.1529/biophysj.108.132035

10. Rapedius M, Paynter JJ, Fowler PW , Sansom MSP, Tucker SJ and Baukrowitz T Control of pH and PIP2 gating in heteromeric Kir4.1/Kir5.1 channels by H-bonding at the helix-bundle crossing (2007) Channels. 1 327-330 doi:10.4161/chan.5176

9. Rapedius M, Fowler PW, Sansom MSP, Tucker SJ and Baukrowitz T. H-Bonding at the Helix-Bundle Crossing Controls Gating in Kir Potassium Channels. (2007) Neuron. 55 602-614 doi:10.1016/j.neuron.2007.07.026

8. Fowler PW, Geroult S, Jha S, Waksman G and Coveney PV. Rapid, accurate and precise calculation of relative binding affinities for the SH2 domain using a computational grid. (2007) J. Chem. Theo. Comput. 3 1193-1202 doi:10.1021/ct6003017

7. Fowler PW*, Balali-Mood K*, Deol SS, Coveney PV and Sansom MSP. Monotopic proteins and lipid bilayers: a comparative study. (2007) Biochemistry 46 3108-3115 doi:10.1021/bi602455n

6. Fowler PW and Coveney PV. A computational protocol for the integration of the monotopic protein prostaglandin H2 synthase into a phospholipid bilayer. (2006) Biophys. J. 91 401-410 doi:10.1529/biophysj.105.077784

5. Fowler PW, Jha S and Coveney PV. Grid-based steered thermodynamic integration accelerates the calculation of binding affinities/free energies. (2005) Phil. Trans. R. Soc. Lond. A 363(1833) 1999-2015 doi:10.1098/rsta.2005.1625

4. Giordanetto F, Fowler PW, Saqi M and Coveney PV. Large scale molecular dynamics of native and mutant dihydroptreoate synthase-sulphanilamide complexes suggests the molecular basis for dihyropteroate synthase drug resistance (2005) Phil. Trans. R. Soc. Lond. A 363(1833) 2055-2073 doi:10.1098/rsta.2005.1629

3. Fowler PW and Coveney PV. Modelling biological complexity: a physical scientist's perspective (2005) J. R. Soc. Interface 2(4) 267-280 doi:10.1098/rsif.2005.0045

2. Fowler PW, Jha S, Coveney PV and Wan S. Exact calculation of peptide-protein binding energies by steered thermodynamic integration using high performance computing grids (2004) In Proceedings of the UK e-Science All Hands Meeting download

1. Al-Mushadani O, Boghosian BM, Coveney PV, Fowler PW, Maillet JB and Wilson JL. Lattice-Gas Simulations of Ternary Amphiphilic Fluid Flow in Porous Media (1998) Int. J. Mod. Phys. C 9 1479 doi:10.1142/S0129183198001345