Genomes and Genes


Mark S P Sansom


Affiliation: University of Oxford
Country: UK


  1. Fowler P, Hélie J, Duncan A, Chavent M, Koldsø H, Sansom M. Membrane stiffness is modified by integral membrane proteins. Soft Matter. 2016;12:7792-7803 pubmed
    ..Our results suggest that integral membrane proteins can have different effects, and in the case of the bacterial outer membrane protein, BtuB, the greater the density of protein, the larger the reduction in stiffness. ..
  2. Ni T, Kalli A, Naughton F, Yates L, Naneh O, Kozorog M, et al. Structure and lipid-binding properties of the kindlin-3 pleckstrin homology domain. Biochem J. 2017;474:539-556 pubmed publisher
  3. Hedger G, Koldsø H, Chavent M, Siebold C, Rohatgi R, Sansom M. Cholesterol Interaction Sites on the Transmembrane Domain of the Hedgehog Signal Transducer and Class F G Protein-Coupled Receptor Smoothened. Structure. 2018;: pubmed publisher
    ..These predictions provide molecular-level insights into cholesterol interactions with a class F GPCR, suggesting potential druggable sites. ..
  4. Song W, Yen H, Robinson C, Sansom M. State-dependent Lipid Interactions with the A2a Receptor Revealed by MD Simulations Using In Vivo-Mimetic Membranes. Structure. 2018;: pubmed publisher
    ..Our results demonstrated that the bound lipids allosterically regulate the functional properties of GPCRs. These protein-lipid interactions provide a springboard for design of allosteric modulators of GPCRs. ..
  5. Rao S, Lynch C, Klesse G, Oakley G, Stansfeld P, Tucker S, et al. Water and hydrophobic gates in ion channels and nanopores. Faraday Discuss. 2018;209:231-247 pubmed publisher
    ..Overall, these results suggest that simulations of the behaviour of water in hydrophobic gates can reveal important design principles for the engineering of gates in novel biomimetic nanopores. ..
  6. Chavent M, Duncan A, Rassam P, Birkholz O, Hélie J, Reddy T, et al. How nanoscale protein interactions determine the mesoscale dynamic organisation of bacterial outer membrane proteins. Nat Commun. 2018;9:2846 pubmed publisher
  7. Stansfeld P, Goose J, Caffrey M, Carpenter E, Parker J, Newstead S, et al. MemProtMD: Automated Insertion of Membrane Protein Structures into Explicit Lipid Membranes. Structure. 2015;23:1350-61 pubmed publisher
  8. Reddy T, Shorthouse D, Parton D, Jefferys E, Fowler P, Chavent M, et al. Nothing to sneeze at: a dynamic and integrative computational model of an influenza A virion. Structure. 2015;23:584-97 pubmed publisher
    ..Our simulations indicate that viral spike proteins do not aggregate and thus are competent for multivalent immunoglobulin G interactions. ..
  9. Aryal P, Sansom M, Tucker S. Hydrophobic gating in ion channels. J Mol Biol. 2015;427:121-30 pubmed publisher
    ..Here we review the evidence for this process and propose that this unusual behavior of water represents an increasingly important element in understanding the relationship between ion channel structure and function. ..

More Information


  1. Abd Halim K, Koldsø H, Sansom M. Interactions of the EGFR juxtamembrane domain with PIP2-containing lipid bilayers: Insights from multiscale molecular dynamics simulations. Biochim Biophys Acta. 2015;1850:1017-25 pubmed publisher
    ..This article is part of a Special Issue entitled Recent developments of molecular dynamics. ..
  2. Yen H, Hoi K, Liko I, Hedger G, Horrell M, Song W, et al. PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling. Nature. 2018;559:423-427 pubmed publisher
    ..These modulating effects of lipids on receptors suggest consequences for understanding function, G-protein selectivity and drug targeting of class A GPCRs. ..
  3. Chavent M, Karia D, Kalli A, Domański J, Duncan A, Hedger G, et al. Interactions of the EphA2 Kinase Domain with PIPs in Membranes: Implications for Receptor Function. Structure. 2018;26:1025-1034.e2 pubmed publisher
    ..Integration of these results with those from previous studies enable computational reconstitution of a near complete EphA2 receptor within a membrane, suggesting a role for receptor-lipid interactions in modulation of EphA2. ..
  4. Hanson S, Newstead S, Swartz K, Sansom M. Capsaicin interaction with TRPV1 channels in a lipid bilayer: molecular dynamics simulation. Biophys J. 2015;108:1425-1434 pubmed publisher
    ..We discuss the significance of capsaicin flipping from the extracellular to the intracellular leaflet and mechanisms of binding site access by capsaicin. ..
  5. Shorthouse D, Hedger G, Koldsø H, Sansom M. Molecular simulations of glycolipids: Towards mammalian cell membrane models. Biochimie. 2016;120:105-9 pubmed publisher
    ..The resultant membrane model is used to simulate the interactions of GM3 with the transmembrane domain of the EGFR. ..
  6. Trick J, Chelvaniththilan S, Klesse G, Aryal P, Wallace E, Tucker S, et al. Functional Annotation of Ion Channel Structures by Molecular Simulation. Structure. 2016;24:2207-2216 pubmed publisher
    ..e., non-conductive) state. We also illustrate the application of water equilibrium density simulations to annotate different conformational states of a glycine receptor. ..
  7. Aryal P, Jarerattanachat V, Clausen M, Schewe M, McClenaghan C, Argent L, et al. Bilayer-Mediated Structural Transitions Control Mechanosensitivity of the TREK-2 K2P Channel. Structure. 2017;25:708-718.e2 pubmed publisher
    ..Overall, this study provides a dynamic structural insight into K2P channel mechanosensitivity and illustrates how the structure of a eukaryotic mechanosensitive ion channel responds to changes in forces within the bilayer. ..
  8. Willems N, Lelimousin M, Skjold Jørgensen J, Svendsen A, Sansom M. The effect of mutations in the lid region of Thermomyces lanuginosus lipase on interactions with triglyceride surfaces: A multi-scale simulation study. Chem Phys Lipids. 2018;211:4-15 pubmed publisher
  9. Naughton F, Kalli A, Sansom M. Modes of Interaction of Pleckstrin Homology Domains with Membranes: Toward a Computational Biochemistry of Membrane Recognition. J Mol Biol. 2017;: pubmed publisher
    ..These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high-affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo. ..
  10. Chavent M, Duncan A, Sansom M. Molecular dynamics simulations of membrane proteins and their interactions: from nanoscale to mesoscale. Curr Opin Struct Biol. 2016;40:8-16 pubmed publisher
    ..Current methods allow near atomic resolution simulations of small membrane organelles, and of enveloped viruses to be performed, revealing key aspects of their structure and functionally important dynamics. ..
  11. Hedger G, Sansom M. Lipid interaction sites on channels, transporters and receptors: Recent insights from molecular dynamics simulations. Biochim Biophys Acta. 2016;1858:2390-2400 pubmed publisher
    ..This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Róg. ..
  12. Reddy T, Sansom M. Computational virology: From the inside out. Biochim Biophys Acta. 2016;1858:1610-8 pubmed publisher
    ..This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. ..
  13. Chavent M, Seiradake E, Jones E, Sansom M. Structures of the EphA2 Receptor at the Membrane: Role of Lipid Interactions. Structure. 2016;24:337-47 pubmed publisher
    ..Altogether, our data suggest that FN2 serves a dual function of interacting with anionic lipids and constraining the structure of the EphA2 ectodomain to adopt membrane-proximal configurations. ..
  14. Kalli A, Rog T, Vattulainen I, Campbell I, Sansom M. The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations. J Membr Biol. 2017;250:337-351 pubmed publisher
    ..This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes. ..
  15. Yamamoto E, Kalli A, Yasuoka K, Sansom M. Interactions of Pleckstrin Homology Domains with Membranes: Adding Back the Bilayer via High-Throughput Molecular Dynamics. Structure. 2016;24:1421-1431 pubmed publisher
    ..This provides a global picture of PH domain interactions with membranes. The high-throughput approach could be extended to other families of peripheral membrane proteins. ..
  16. Willems N, Lelimousin M, Koldsø H, Sansom M. Interfacial activation of M37 lipase: A multi-scale simulation study. Biochim Biophys Acta Biomembr. 2017;1859:340-349 pubmed publisher
    ..The exposure of hydrophobic residues within lid and active site flap regions (residues 94-110) during the activation process provides insights into the functional effect of hydrophobic surfaces on lipase activation. ..
  17. Duncan A, Reddy T, Koldsø H, Hélie J, Fowler P, Chavent M, et al. Protein crowding and lipid complexity influence the nanoscale dynamic organization of ion channels in cell membranes. Sci Rep. 2017;7:16647 pubmed publisher
    ..This interplay between the diffusion and the dynamic organization of Kir channels may have important implications for channel function. ..
  18. Reddy T, Sansom M. The Role of the Membrane in the Structure and Biophysical Robustness of the Dengue Virion Envelope. Structure. 2016;24:375-82 pubmed publisher
    ..Biophysical robustness of the envelope may confer resilience to environmental perturbations. ..