Simon G. Patching, Ph.D.

 

SIMON PATCHING

 

 

 

 

 

 

Independent Researcher, Leeds, UK

  • Biography
  • Research Interests
  • Publications

Simon Patching has a B.Sc. (Hons) degree in Biomedical Chemistry and a Ph.D. in Chemistry, industrial experience and extensive academic research, teaching, supervisory, publishing, refereeing and organisational experience in structure-function studies of membrane proteins and other drug targets using a wide range of chemical, biochemical, biophysical, molecular imaging and computational techniques.  A major emphasis has been development and application of nuclear magnetic resonance (NMR) including isotope labelling and sample preparation strategies.  Associated expertise includes membrane protein production (cloning, expression, mutation, solubilisation, purification, reconstitution, analysis of structural and functional integrity and stability), design, synthesis and analytical and molecular characterisation of novel and isotope-labelled compounds (stable isotopes, radiolabels, deuteration, spin labels), microbiological techniques, assay development, kinetic and dynamic analyses.  He has made major contributions to multiple UK-based research council, industry and charity funded research projects and to EU-funded research consortia, with expansions to worldwide collaborative research.

 

His research interests span a number of themes including Biomedical Chemistry, Molecular Membrane Biology, Biomolecular NMR, Biophysics, Medical Physics, Medical Technology, Nuclear Medicine, Biological and Biomedical Engineering, Electronic Engineering, Oral Microbiology, Antibiotic Resistance, Drug Discovery.  All of these are linked through an expanding network for development and application of existing and novel technologies to study structure, function, ligand recognition, molecular mechanism, dynamics and multidimensional relationships of membrane proteins, other drug targets and molecular markers of health and disease.

Key publications

Ahmad I, Nawaz N, Darwesh NM, ur Rahman S, Mustafa MZ, Khan SB, Patching SG. Overcoming challenges for amplified expression of recombinant proteins using Escherichia coli. Protein Expr Purif 2018; 144: 12-18.

Saidijam M, Karimi Dermani F, Sohrabi S, Patching SG. Efflux proteins at the blood-brain barrier: review and bioinformatics analysis. Xenobiotica 2018; 48(5): 506-532.

Saidijam M, Afshar F, Ahmad I, Patching SG. Nucleoside transporters in PET imaging of proliferating cancer cells using 3ꞌ-deoxy-3ꞌ-[18F]fluoro-L-thymidine. Journal of Diagnostic Imaging in Therapy. 2018; 5(1):1-13.

Saidijam M, Azizpour S, Patching SG. Comprehensive analysis of the numbers, lengths and amino acid compositions of transmembrane helices in prokaryotic, eukaryotic and viral integral membrane proteins of high-resolution structure. J Biomol Struct Dyn 2018; 36(2): 443-464.

Sun L, Xie H, Ingram JC, Hope RJ, Baldwin SA, Patching SG. Characterization of the Escherichia coli concentrative nucleoside transporter NupC using computational, biochemical and biophysical methods. Biochemistry. 2017 [Epub ahead of print] DOI: 10.1021/acs.biochem.7b00172.

Saidijam M, Karimi Dermani F, Sohrabi S, Patching SG. Efflux proteins at the blood-brain barrier: review and bioinformatics analysis. Xenobiotica. 2017 [Epub ahead of print] DOI:  10.1080/00498254.2017.1328148.

Rahman M, Ismat F, Jiao L, Baldwin JM, Sharples DJ, Baldwin SA, Patching SG. Characterisation of the DAACS family Escherichia coli glutamate/aspartate-proton symporter GltP using computational, chemical, biochemical and biophysical methods. J Membr Biol. 2017;250(2): 145-162.

Patching SG. Glucose transporters at the blood-brain barrier: Function, regulation and gateways for drug delivery. Mol Neurobiol. 2017;54(2): 1046-1077.

Phillips-Jones MK, Channell G, Kelsall CJ, Hughes CS, Ashcroft AE, Patching SG, Dinu V, Gillis RB, Adams GG, Harding SE. Hydrodynamics of the VanA-type VanS histidine kinase: an extended solution conformation and first evidence for interactions with vancomycin. Sci Rep. 2017;7: 46180.

Saidijam M, Azizpour S, Patching SG. Comprehensive analysis of the numbers, lengths and amino acid compositions of transmembrane helices in prokaryotic, eukaryotic and viral integral membrane proteins of high-resolution structure. J Biomol Struct Dyn. 2017 [Epub ahead of print] DOI: 10.1080/07391102.2017.1285725.

Patching SG. Synthesis, NMR analysis and applications of isotope-labelled hydantoins. Journal of Diagnostic Imaging in Therapy. 2017;4(1): 3-26.

Saidijam M, Azizpour S, Patching SG. Amino acid composition analysis of human secondary transport proteins and implications for reliable membrane topology prediction. J Biomol Struct Dyn. 2017;35(5): 929-949.

Patching SG. NMR-active nuclei for biological and biomedical applications. Journal of Diagnostic Imaging in Therapy. 2016; 3(1): 7-48.

Hussain R, Harding SE, Hughes CS, Ma P, Patching SG, Edara S, Siligardi G, Henderson PJ, Phillips-Jones MK. Purification of bacterial membrane sensor kinases and biophysical methods for determination of their ligand and inhibitor interactions. Biochem Soc Trans. 2016;44(3): 810-823.

Saidijam M, Azizpour S, Patching SG. Amino acid composition analysis of human secondary transport proteins and implications for reliable membrane topology prediction. J Biomol Struct Dyn. 2016 [Epub ahead of print] 10.1080/07391102.2016.1167622

Ma P, Patching SG, Ivanova E, Baldwin JM, Sharples D, Baldwin SA, Henderson PJ. Allantoin transport protein, PucI, from Bacillus subtilis: evolutionary relationships, amplified expression, activity and specificity. Microbiology. 2016;162(5): 823-836.

Patching SG. Glucose transporters at the blood-brain barrier: Function, regulation and gateways for drug delivery. Mol Neurobiol. 2016 [Epub ahead of print] DOI: 10.1007/s12035-015-9672-6

Patching SG. Solid-state NMR structures of integral membrane proteins.  Mol Membr Biol. 2015;32(5-8): 156-178.

Hiruma-Shimizu K, Shimizu H, Thompson GS, Kalverda AP, Patching SG. Deuterated detergents for structural and functional studies of membrane proteins: Properties, chemical synthesis and applications. Mol Membr Biol. 2015;32(5-8): 139-155.

Patching SG. Roles of facilitative glucose transporter GLUT1 in [18F]FDG positron emission tomography (PET) imaging of human diseases. Journal of Diagnostic Imaging in Therapy. 2015; 2(1): 30-102.

Saidijam M, Patching SG. Amino acid composition analysis of secondary transport proteins from Escherichia coli with relation to functional classification, ligand specificity and structure. J Biomol Struct Dyn. 2015; 14: 1-16. [Epub ahead of print]

Whittaker CA, Patching SG, Esmann M, Middleton DA. Ligand orientation in a membrane-embedded receptor site revealed by solid-state NMR with paramagnetic relaxation enhancement. Org Biomol Chem. 2015; 13(9): 2664-2668.

Hiruma-Shimizu K, Kalverda AP, Henderson PJ, Homans SW, Patching SG. Synthesis of uniformly deuterated n-dodecyl-β-D-maltoside (d39-DDM) for solubilization of membrane proteins in TROSY NMR experiments. J Labelled Comp Radiopharm. 2014; 57(14): 737-743.

Simmons KJ, Jackson SM, Brueckner F, Patching SG, Beckstein O, Ivanova E, Geng T, Weyand S, Drew D, Lanigan J, Sharples DJ, Sansom MS, Iwata S, Fishwick CW, Johnson AP, Cameron AD, Henderson PJ. Molecular mechanism of ligand recognition by membrane transport protein, Mhp1. EMBO J. 2014; 33(16): 1831-1844.

Kalverda AP, Gowdy J, Thompson GS, Homans SW, Henderson PJ, Patching SG. TROSY NMR with a 52 kDa sugar transport protein and the binding of a small-molecule inhibitor. Mol Membr Biol. 2014; 31(4): 131-140.

Patching SG. Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery. Biochim Biophys Acta – Biomembranes. 2014; 1838(1 PtA): 43-55.

Siligardi G, Hussain R, Patching SG, Phillips-Jones MK. Ligand- and drug-binding studies of membrane proteins revealed through circular dichroism spectroscopy. Biochim Biophys Acta – Biomembranes. 2014; 1838(1 PtA): 34-42.

Hassan KA, Jackson SM, Penesyan A, Patching SG, Tetu SG, Eijkelkamp BA, Brown MH, Henderson PJ, Paulsen IT. Transcriptomic and biochemical analyses identify a family of chlorhexidine efflux proteins. Proc Natl Acad Sci U S A. 2013; 110(50): 20254-20259.

Middleton DA, Patching SG. Solid-state NMR spectroscopy in drug design and discovery In: Andrushko V, Andrushko N, eds. Stereoselective synthesis of drugs and natural products. Chichester, UK: John Wiley & Sons, Ltd; 2013 (Chapter 51).

Patching SG, Henderson PJ, Sharples DJ, Middleton DA. Probing the contacts of a low-affinity substrate with a membrane-embedded transport protein using 1H-13C cross-polarisation magic-angle spinning solid-state NMR. Mol Membr Biol. 2013; 30(2): 129-137.

Bettaney KE, Sukumar P, Hussain R, Siligardi G, Henderson PJ, Patching SG. A systematic approach to the amplified expression, functional characterization and purification of inositol transporters from Bacillus subtilis. Mol Membr Biol. 2013; 30(1): 3-14.

Phillips-Jones MK, Patching SG, Edara S, Nakayama J, Hussain R, Siligardi G. Interactions of the intact FsrC membrane histidine kinase with the tricyclic peptide inhibitor siamycin I revealed through synchrotron radiation circular dichroism. Phys Chem Chem Phys. 2013; 15(2): 444-447.

Patching SG, Middleton DA, Kalverda AP, Gowdy J, Baldwin SA, Phillips-Jones MK, Levitt MH, Homans SW, Henderson PJF. NMR methods for structure-function investigation of membrane proteins and their ligands. J Labelled Comp Radiopharm. 2012; 55: 132-133.

Patching SG, Jackson S, Simmons KJ, Ma P, Baldwin SA, Johnson AP, Fishwick CWG, Henderson PJF. Isotope chemistry for investigating ligand binding and transport by Mhp1 and its homologues. J Labelled Comp Radiopharm. 2012; 55: 132.

Patching SG, Edara S, Ma P, Nakayama J, Hussain R, Siligardi G, Phillips-Jones MK. Interactions of the intact FsrC membrane histidine kinase with its pheromone ligand GBAP revealed through synchrotron radiation circular dichroism. Biochim Biophys Acta – Biomembranes. 2012; 1818(7): 1595-1602.

Patching SG. NMR structures of polytopic integral membrane proteins. Mol Membr Biol. 2011; 28(6): 370-397.

Patching SG. Efficient syntheses of 13C- and 14C-labelled 5-benzyl and 5-indolylmethyl L-hydantoins. J Labelled Comp Radiopharm. 2011; 54(2): 110-114.

Miller K, Dunsmore CJ, Leeds JA, Patching SG, Sachdeva M, Blake KL, Stubbings WJ, Simmons KJ, Henderson PJ, De Los Angeles J, Fishwick CW, Chopra I. Benzothioxalone derivatives as novel inhibitors of UDP-N-acetylglucosamine enolpyruvyl transferases (MurA and MurZ). J Antimicrob Chemother. 2010; 65(12): 2566-2573.

Patching SG. Synthesis of highly pure 14C-labelled DL-allantoin and 13C NMR analysis of labelling integrity. J Labelled Comp Radiopharm. 2009; 52(9): 401-404.

Patching SG, Edwards R, Middleton DA. Structural analysis of uniformly 13C-labelled solids from selective angle measurements at rotational resonance. J Magn Reson. 2009; 199(2): 242-246.

Rahman M, Patching SG, Ismat F, Henderson PJ, Herbert RB, Baldwin SA, McPherson MJ. Probing metal ion substrate-binding to the E. coli ZitB exporter in native membranes by solid state NMR. Mol Membr Biol. 2008; 25(8): 683-690.

Weyand S, Shimamura T, Yajima S, Suzuki S, Mirza O, Krusong K, Carpenter EP, Rutherford NG, Hadden JM, O’Reilly J, Ma P, Saidijam M, Patching SG, Hope RJ, Norbertczak HT, Roach PC, Iwata S, Henderson PJ, Cameron AD. Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter. Science. 2008; 322(5902): 709-713.

Patching SG, Psakis G, Baldwin SA, Baldwin J, Henderson PJ, Middleton DA. Relative substrate affinities of wild-type and mutant forms of the Escherichia coli sugar transporter GalP determined by solid-state NMR. Mol Membr Biol. 2008; 25(6-7): 474-484.

Dunsmore CJ, Miller K, Blake KL, Patching SG, Henderson PJ, Garnett JA, Stubbings WJ, Phillips SE, Palestrant DJ, Angeles Jde L, Leeds JA, Chopra I, Fishwick CW. 2-Aminotetralones: novel inhibitors of MurA and MurZ. Bioorg Med Chem Lett. 2008; 18(5): 1730-1734.

Middleton DA, Baldwin SA, Herbert RB, Henderson PJF, Patching SG. Exploiting isotope labelling for solid-state NMR studies of drugs and their targets. J Labelled Comp Radiopharm. 2008; 51: 249.

Roach PCJ, O’Reilly J, Norbertczak HT, Hope RJ, Venter H, Patching SG, Jamshad M, Peter G. Stockley PG, Baldwin SA, Herbert RB, Rutherford NG, Bill RM, Henderson PJF. Equipping a research scale fermentation laboratory for production of membrane proteins In: McNeil B, Harvey LM, eds. Practical fermentation technology.  Chichester, UK: John Wiley & Sons, Ltd; 2008 (Chapter 3): 37-67.

Patching SG, Henderson PJ, Herbert RB, Middleton DA. Solid-state NMR spectroscopy detects interactions between tryptophan residues of the E. coli sugar transporter GalP and the alpha-anomer of the D-glucose substrate. J Am Chem Soc. 2008; 130(4): 1236-1244.

Clough J, Saidijam M, Bettaney KE, Szakonyi G, Patching SG, Mueller J, Shibayama K, Bacon M, Barksby E, Groves M, Herbert RB, Phillips-Jones M, Ward A, Gunn-Moore F, O’Reilly J, Rutherford NG, Bill R, Henderson PJF. Prokaryotic membrane transport proteins: amplified expression and purification In Lundstrom KH, ed. Structural genomics on membrane proteins. Taylor and Francis; 2006: 21-42.

Patching SG, Baldwin SA, Baldwin AD, Young JD, Gallagher MP, Henderson PJ, Herbert RB. The nucleoside transport proteins, NupC and NupG, from Escherichia coli: specific structural motifs necessary for the binding of ligands. Org Biomol Chem. 2005; 3(3): 462-470.

Saidijam M, Bettaney KE, Szakonyi G, Psakis G, Shibayama K, Suzuki S, Clough JL, Blessie V, Abu-Bakr A, Baumberg S, Meuller J, Hoyle CK, Palmer SL, Butaye P, Walravens K, Patching SG, O’reilly J, Rutherford NG, Bill RM, Roper DI, Phillips-Jones MK, Henderson PJ. Active membrane transport and receptor proteins from bacteria. Biochem Soc Trans. 2005; 33(Pt 4): 867-872.

Xie H, Patching SG, Gallagher MP, Litherland GJ, Brough AR, Venter H, Yao SY, Ng AM, Young JD, Herbert RB, Henderson PJ, Baldwin SA. Purification and properties of the Escherichia coli nucleoside transporter NupG, a paradigm for a major facilitator transporter sub-family. Mol Membr Biol. 2004; 21(5): 323-336.

Patching SG, Brough AR, Herbert RB, Rajakarier JA, Henderson PJ, Middleton DA. Substrate affinities for membrane transport proteins determined by 13C cross-polarization magic-angle spinning nuclear magnetic resonance spectroscopy. J Am Chem Soc. 2004; 126(10): 3072-3080.

Patching SG, Herbert RB, O’Reilly J, Brough AR, Henderson PJ. Low 13C-background for NMR-based studies of ligand binding using 13C-depleted glucose as carbon source for microbial growth: 13C-labeled glucose and 13C-forskolin binding to the galactose-H+ symport protein GalP in Escherichia coli. J Am Chem Soc. 2004; 126(1): 86-87.

Patching SG, Herbert RB, Henderson PJF, Brough AR, Middleton DA. Stable isotopes and membrane transport proteins: chemical synthesis and biochemical analysis by solid state NMR. J Labelled Comp Radiopharm. 2004; 47: 303.

Patching SG, Middleton DA, Henderson PJ, Herbert RB. The economical synthesis of [2′-13C, 1,3-15N2]uridine; preliminary conformational studies by solid state NMR. Org Biomol Chem. 2003; 1(12): 2057-2062.

Patching SG, Henderson PJF, Spooner PJR, Watts A, Baldwin SA, Herbert RB.  A solid-state NMR approach to the structure-activity relationship of the nucleoside transport protein NupC of Escherichia coli. Biochem Soc Trans. 2000; 28: A89.

Patching SG, Gardiner PH. Recent developments in selenium metabolism and chemical speciation: a review. J Trace Elem Med Biol. 1999; 13(4): 193-214.