The Martini model has been succesfully applied to simulate protein-lipid interactions, with early examples showing how lipid membrane composition affects the self-assembly of GPCRs [1], glycophorin [2] ,and more [3,4], or the gating behavior of mechanosenstive channels [5]. More recent examples include the salt-dependent binding of actin filaments to charged membranes [17] and the lipid-dependent toppling mechanism of the energy coupling tranpsort factor [16].
Over the past decade, many more specific lipid binding sites have been resolved based on Martini simulations, including binding sites for cardiolipins [6,7], gangliosides [8], galactolipids [9,10], PIPs [11,12,20,21], ceramides [13], anionic lipids [14], cholesterol [15], and many more - recently reviewed in [19]. A recent development is to study protein-lipid interactions in more complex environments, such as the plasma membrane, giving rise to the concept of protein-lipid fingerprints [18, see Figure].
[3] L.V. Schafer, D.H. de Jong, A. Holt, A.J. Rzepiela, A.H. de Vries, B. Poolman, J.A. Killian, S.J. Marrink. Lipid packing drives the segregation of transmembrane helices into disordered lipid domains in model biomembranes. PNAS, 108:1343-1348, 2011.
open access
[4] D.H. de Jong, C.A. Lopez, S.J. Marrink. Molecular view on protein sorting into liquid-ordered membrane domains mediated by gangliosides and lipid anchors. Farad. Discuss., 161:347-363, 2013. abstract
[5] N. Mukherjee, M.D. Jose, J.P. Birkner, M. Walko, H.I. Ingólfsson, A. Dimitrova, C. Arnarez, S.J. Marrink, A. Koçer. The activation mode of the mechanosensitive ion channel, MscL, by lysophosphatidylcholine differs from tension-induced gating. FASEB J., 28:4292-4302, 2014. abstract
[6] C. Arnarez, J.P. Mazat, J. Elezgaray, S.J. Marrink, X. Periole. Evidence for cardiolipin binding sites on the membrane-exposed surface of the cytochrome bc1. JACS, 135:3112–3120, 2013. open access
[7] C. Arnarez, S.J. Marrink, X. Periole. Identification of cardiolipin binding sites on cytochrome c oxidase at the entrance of proton channels. Sci. Rep., 3:1263, 2013. open access
[8] R.X. Gu, H.I. Ingólfsson, A.H. de Vries, S.J. Marrink, D.P. Tieleman. Ganglioside-lipid and ganglioside-protein interactions revealed by coarse-grained and atomistic molecular dynamics simulations. JPCB, 121:3262–3275, 2017. open access
[9] F.J. van Eerden, M.N. Melo, P.W.J.M. Frederix, S.J. Marrink. Prediction of thylakoid lipid binding sites on photosystem II. Biophys. J. 113:2669-2681, 2017. open access
[10] S. Thallmair, P.A. Vainikka, S.J. Marrink. Lipid Fingerprints and Cofactor Dynamics of Light-Harvesting Complex II in Different Membranes. Biophys. J., 116:1446-1455, 2019. doi:10.1016/j.bpj.2019.03.009
[11] F. Sun, C.F.E. Schroer, L. Xu, H. Yin, S.J. Marrink, S.Z. Luo. Molecular Dynamics of the Association of L-Selectin and FERM Regulated by PIP2. Biophys. J., 114:1858–1868, 2018. doi:10.1016/j.bpj.2018.02.034
[12] F. Sun, C.F.E. Schroer, C.R. Palacios, L. Xu, S.Z. Luo, S.J. Marrink. Molecular mechanism for bidirectional regulation of CD44 for lipid raft affiliation by palmitoylations and PIP2. PLoS Comput. Biol. 16:e1007777, 2020. doi.org/10.1371/journal.pcbi.1007777
[13] S. Dadsena, S. Bockelmann, J.G.M. Mina, D.G. Hassan, S. Korneev, G. Razzera, H. Jahn, P. Niekamp, D. Müller, M. Schneider, F.G. Tafesse, S.J. Marrink, M.N. Melo, J.C.M. Holthuis, Ceramides bind VDAC2 to trigger mitochondrial apoptosis. Nature Commun. 10:1832, 2019. doi:10.1038/s41467-019-09654
[14] S. Koch, `M. Exterkate, C.A. López, M. Patro, S.J. Marrink, A.J.M. Driessen Two distinct anionic phospholipid-dependent events involved in SecA-mediated protein translocation. BBA-Biomembr. 1861, 183035, 2019. doi.10.1016/j.bbamem.2019.183035
[15] A. Buyan, C.D. Cox, J. Barnoud, J. Li, H.S.M. Chan, B. Martinac, S.J. Marrink, B. Corry. Piezo1 forms specific, functionally important interactions with phosphoinositides and cholesterol. Biophys. J. 119:1683-1697, 2020. doi.10.1016/j.bpj.2020.07.043
[16] I. Faustino, H. Abdizadeh, P.C.T. Souza, A. Jeucken, W.K. Stanek, A. Guskov, D.J. Slotboom, S.J. Marrink. Membrane mediated toppling mechanism of the folate energy coupling factor transporter. Nature Commun. 11:1763, 2020. doi.org/10.1038/s41467-020-15554-9
[17] C.F.E. Schroer, L. Baldauf, L. van Buren, T.A. Wassenaar, M.N. Melo, G. Koenderink, S.J. Marrink. Charge-dependent interactions of monomeric and filamentous actin with lipid bilayers. PNAS, 117: 5861-5872, 2020. doi.org/10.1073/pnas.1914884117
[18] V. Corradi, E. Mendez-Villuendas, H.I. Ingólfsson, R.X. Gu, I. Siuda, M.N. Melo, A. Moussatova, L.J. DeGagné, B.I. Sejdiu, G. Singh, T.A. Wassenaar, K. Delgado Magnero, S.J. Marrink, D.P. Tieleman. Lipid–Protein Interactions Are Unique Fingerprints for Membrane Proteins. ACS Central Science 4:709–717, 2018. doi:10.1021/acscentsci.8b00143
[19] V. Corradi, B.I. Sejdiu, H. Mesa-Galloso, H. Abdizadeh, S.Y. Noskov, S.J. Marrink, D.P. Tieleman. Emerging Diversity in Lipid–Protein Interactions, Chem. Review, 119:5775–5848, 2019. doi:10.1021/acs.chemrev.8b00451
[20] V. Thallmair, L. Schultz, W. Zhao, S.J. Marrink, D. Oliver, S. Thallmair. Two cooperative binding sites sensitize PI(4,5)P2 recognition by the tubby domain. Science Advances 8 (36), eabp9471, 2022. DOI: 10.1126/sciadv.abp9471
[21] M. Ren, L. Zhao, Z. Ma, H. An, S.J. Marrink, F. Sun. Molecular basis of PIP2-dependent conformational switching of phosphorylated CD44 in binding FERM. Biophys. J., 122 (13), 2675-2685, 2023. doi:10.1016/j.bpj.2023.05.021