Transport mechanism of DgoT, a bacterial homolog of SLC17 organic anion transporters.
Major Facilitator Superfamily
Molecular Dynamics Simulations
Organic Anion Transporter
Proton-coupled Secondary Transport
Solid-supported Membrane Electrophysiology
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
25 Oct 2024
25 Oct 2024
Historique:
received:
19
03
2024
accepted:
07
10
2024
revised:
01
10
2024
medline:
26
10
2024
pubmed:
26
10
2024
entrez:
25
10
2024
Statut:
aheadofprint
Résumé
The solute carrier 17 (SLC17) family contains anion transporters that accumulate neurotransmitters in secretory vesicles, remove carboxylated monosaccharides from lysosomes, or extrude organic anions from the kidneys and liver. We combined classical molecular dynamics simulations, Markov state modeling and hybrid first principles quantum mechanical/classical mechanical (QM/MM) simulations with experimental approaches to describe the transport mechanisms of a model bacterial protein, the D-galactonate transporter DgoT, at atomic resolution. We found that protonation of D46 and E133 precedes galactonate binding and that substrate binding induces closure of the extracellular gate, with the conserved R47 coupling substrate binding to transmembrane helix movement. After isomerization to an inward-facing conformation, deprotonation of E133 and subsequent proton transfer from D46 to E133 opens the intracellular gate and permits galactonate dissociation either in its unprotonated form or after proton transfer from E133. After release of the second proton, apo DgoT returns to the outward-facing conformation. Our results provide a framework to understand how various SLC17 transport functions with distinct transport stoichiometries can be attained through subtle variations in proton and substrate binding/unbinding.
Identifiants
pubmed: 39455803
doi: 10.1038/s44318-024-00279-y
pii: 10.1038/s44318-024-00279-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : AL 2511/1-2
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : CA 973/27-2
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : FA 301/15-2
Informations de copyright
© 2024. The Author(s).
Références
Abraham MJ, Murtola T, Schulz R, Páll S, Smith JC, Hess B, Lindahl E (2015) GROMACS: high performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1–2:19–25. https://doi.org/10.1016/j.softx.2015.06.001
doi: 10.1016/j.softx.2015.06.001
Barducci A, Bussi G, Parrinello M (2008) Well-tempered metadynamics: a smoothly converging and tunable free-energy method. Phys Rev Lett 100(2):020603. https://doi.org/10.1103/PhysRevLett.100.020603
doi: 10.1103/PhysRevLett.100.020603
pubmed: 18232845
Batarni S, Nayak N, Chang A, Li F, Hareendranath S, Zhou L, Xu H, Stroud R, Eriksen J, Edwards RH (2023) Substrate recognition and proton coupling by a bacterial member of solute carrier family 17. J Biol Chem. https://doi.org/10.1016/j.jbc.2023.104646
Bazzone A, Barthmes M, Fendler K (2017) SSM-based electrophysiology for transporter research. Methods Enzymol 594:31–83. https://doi.org/10.1016/bs.mie.2017.05.008
doi: 10.1016/bs.mie.2017.05.008
pubmed: 28779843
Bazzone A, Tesmer L, Kurt D, Kaback HR, Fendler K, Madej MG (2021) Investigation of sugar binding kinetics of the E. coli sugar/H
doi: 10.1016/j.jbc.2021.101505
pubmed: 34929170
pmcid: 8784342
Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev Gen Phys 38(6):3098–3100. https://doi.org/10.1103/physreva.38.3098
doi: 10.1103/physreva.38.3098
Berendsen HJC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81(8):3684–3690. https://doi.org/10.1063/1.448118
doi: 10.1063/1.448118
Bolnykh V, Olsen JMH, Meloni S, Bircher MP, Ippoliti E, Carloni P, Rothlisberger U (2019) Extreme scalability of DFT-based QM/MM MD simulations using MiMiC. J Chem Theory Comput 15(10):5601–5613. https://doi.org/10.1021/acs.jctc.9b00424
doi: 10.1021/acs.jctc.9b00424
pubmed: 31498615
Bosshart PD, Kalbermatter D, Bonetti S, Fotiadis D (2019) Mechanistic basis of L-lactate transport in the SLC16 solute carrier family. Nat Commun 10(1):2649. https://doi.org/10.1038/s41467-019-10566-6
doi: 10.1038/s41467-019-10566-6
pubmed: 31201333
pmcid: 6573034
Bulo RE, Ensing B, Sikkema J, Visscher L (2009) Toward a practical method for adaptive QM/MM simulations. J Chem Theory Comput 5(9):2212–2221. https://doi.org/10.1021/ct900148e
doi: 10.1021/ct900148e
pubmed: 26616607
Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014101. https://doi.org/10.1063/1.2408420
doi: 10.1063/1.2408420
pubmed: 17212484
Chiariello MG, Alfonso-Prieto M, Ippoliti E, Fahlke C, Carloni P (2021) Mechanisms underlying proton release in CLC-type F
doi: 10.1021/acs.jpclett.1c00361
pubmed: 33950673
Chiariello MG, Bolnykh V, Ippoliti E, Meloni S, Olsen JMH, Beck T, Rothlisberger U, Fahlke C, Carloni P (2020) Molecular basis of CLC antiporter inhibition by fluoride. J Am Chem Soc 142(16):7254–7258. https://doi.org/10.1021/jacs.9b13588
doi: 10.1021/jacs.9b13588
pubmed: 32233472
Ciccotti G, Ferrario M (2004) Blue moon approach to rare events. Mol Simul 30(11–12):787–793. https://doi.org/10.1080/0892702042000270214
doi: 10.1080/0892702042000270214
Ciccotti G, Kapral R, Vanden-Eijnden E (2005) Blue moon sampling, vectorial reaction coordinates, and unbiased constrained dynamics. Chemphyschem Eur J Chem Phys Phys Chem 6(9):1809–1814. https://doi.org/10.1002/cphc.200400669
doi: 10.1002/cphc.200400669
Dama JF, Parrinello M, Voth GA (2014) Well-tempered metadynamics converges asymptotically. Phys Rev Lett 112(24):240602. https://doi.org/10.1103/PhysRevLett.112.240602
doi: 10.1103/PhysRevLett.112.240602
pubmed: 24996077
Dang S, Sun L, Huang Y, Lu F, Liu Y, Gong H, Wang J, Yan N (2010) Structure of a fucose transporter in an outward-open conformation. Nature 467(7316):734–738. https://doi.org/10.1038/nature09406
doi: 10.1038/nature09406
pubmed: 20877283
Daura X, Gademann K, Jaun B, Seebach D, van Gunsteren WF, Mark AE (1999) Peptide folding: when simulation meets experiment. Angew Chem Int Ed 38(1–2):236–240. https://doi.org/10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M
doi: 10.1002/(SICI)1521-3773(19990115)38:1/2<236::AID-ANIE236>3.0.CO;2-M
Deacon J, Cooper RA (1977) D-Galactonate utilisation by enteric bacteria. The catabolic pathway in Escherichia coli. FEBS Lett 77(2):201–205. https://doi.org/10.1016/0014-5793(77)80234-2
doi: 10.1016/0014-5793(77)80234-2
pubmed: 324806
Deuflhard P, Weber M (2005) Robust Perron cluster analysis in conformation dynamics. Linear Algebra Appl 398:161–184. https://doi.org/10.1016/j.laa.2004.10.026
doi: 10.1016/j.laa.2004.10.026
Drew D, North RA, Nagarathinam K, Tanabe M (2021) Structures and general transport mechanisms by the major facilitator superfamily (MFS). Chem Rev 121(9):5289–5335. https://doi.org/10.1021/acs.chemrev.0c00983
Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG (1995) A smooth particle mesh Ewald method. J Chem Phys 103(19):8577–8593. https://doi.org/10.1063/1.470117
doi: 10.1063/1.470117
Feng J, Selvam B, Shukla D (2021) How do antiporters exchange substrates across the cell membrane? An atomic-level description of the complete exchange cycle in NarK. Structure 29(8):922–933.e3. https://doi.org/10.1016/j.str.2021.03.014
doi: 10.1016/j.str.2021.03.014
pubmed: 33836147
Hohenberg P, Kohn W (1964) Inhomogeneous electron gas. Phys Rev 136(3B):B864–B871. https://doi.org/10.1103/PhysRev.136.B864
doi: 10.1103/PhysRev.136.B864
Hoover WG (1985) Canonical dynamics: equilibrium phase-space distributions. Phys Rev A 31(3):1695–1697. https://doi.org/10.1103/PhysRevA.31.1695
doi: 10.1103/PhysRevA.31.1695
Hu W, Chi C, Song K, Zheng H (2023) The molecular mechanism of sialic acid transport mediated by Sialin. Sci Adv 9(3):eade8346. https://doi.org/10.1126/sciadv.ade8346
doi: 10.1126/sciadv.ade8346
pubmed: 36662855
pmcid: 9858498
Huang J, Rauscher S, Nawrocki G, Ran T, Feig M, de Groot BL, Grubmüller H, MacKerell AD (2017) CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat Methods 14(1):71–73. https://doi.org/10.1038/nmeth.4067
doi: 10.1038/nmeth.4067
pubmed: 27819658
Husic BE, Pande VS (2018) Markov state models: from an art to a science. J Am Chem Soc 140(7):2386–2396. https://doi.org/10.1021/jacs.7b12191
doi: 10.1021/jacs.7b12191
pubmed: 29323881
Hutter J, Alavi A, Deutsch T, Bernasconi M, Goedecker S, Marx D, Tuckerman M, Parrinello M (2000) CPMD, Copyright IBM Corp., 1990–2019, Copyright MPI für Festkörperforschung, Stuttgart 1997–2001. http://www.cpmd.org/ .
Iharada M, Miyaji T, Fujimoto T, Hiasa M, Anzai N, Omote H, Moriyama Y (2010) Type 1 sodium-dependent phosphate transporter (SLC17A1 protein) is a Cl
doi: 10.1074/jbc.M110.122721
pubmed: 20566650
pmcid: 2924012
Ishikawa T, Nishikawa H, Gao Y, Sawa Y, Shibata H, Yabuta Y, Maruta T, Shigeoka S (2008) The pathway via D-galacturonate/L-galactonate is significant for ascorbate biosynthesis in Euglena gracilis: identification and functional characterization of aldonolactonase. J Biol Chem 283(45):31133–31141. https://doi.org/10.1074/jbc.M803930200
doi: 10.1074/jbc.M803930200
pubmed: 18782759
pmcid: 2662179
Kaback HR, Guan L (2019) It takes two to tango: the dance of the permease. J Gen Physiol 151(7):878–886. https://doi.org/10.1085/jgp.201912377
doi: 10.1085/jgp.201912377
pubmed: 31147449
pmcid: 6605686
Kaiser S, Yue Z, Peng Y, Nguyen TD, Chen S, Teng D, Voth GA (2024) Molecular dynamics simulation of complex reactivity with the rapid approach for proton transport and other reactions (RAPTOR) software package. J Phys Chem B 128(20):4959–4974. https://doi.org/10.1021/acs.jpcb.4c01987
doi: 10.1021/acs.jpcb.4c01987
pubmed: 38742764
Klauda JB, Venable RM, Freites JA, O’Connor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114(23):7830–7843. https://doi.org/10.1021/jp101759q
doi: 10.1021/jp101759q
pubmed: 20496934
pmcid: 2922408
Kohn W, Sham LJ (1965) Self-consistent equations including exchange and correlation effects. Phys Rev 140(4A):A1133–A1138. https://doi.org/10.1103/PhysRev.140.A1133
doi: 10.1103/PhysRev.140.A1133
Kolen B, Borghans B, Kortzak D, Lugo V, Hannack C, Guzman RE, Ullah G, Fahlke C (2023) Vesicular glutamate transporters are H
doi: 10.1038/s41467-023-38340-9
pubmed: 37169755
pmcid: 10175566
Kostritskii AY, Alleva C, Cönen S, Machtens J-P (2021) g_elpot: a tool for quantifying biomolecular electrostatics from molecular dynamics trajectories. J Chem Theory Comput 17(5):3157–3167. https://doi.org/10.1021/acs.jctc.0c01246
doi: 10.1021/acs.jctc.0c01246
pubmed: 33914551
Kostritskii AY, Machtens J-P (2023) Domain- and state-specific shape of the electric field tunes voltage sensing in voltage-gated sodium channels. Biophys J 122(10):1807–1821. https://doi.org/10.1016/j.bpj.2023.04.013
doi: 10.1016/j.bpj.2023.04.013
pubmed: 37077046
pmcid: 10209041
Kumar H, Finer-Moore JS, Kaback HR, Stroud RM (2015) Structure of LacY with an α-substituted galactoside: connecting the binding site to the protonation site. Proc Natl Acad Sci USA 112(29):9004–9009. https://doi.org/10.1073/pnas.1509854112
doi: 10.1073/pnas.1509854112
pubmed: 26157133
pmcid: 4517220
Laio A, VandeVondele J, Rothlisberger U (2002) A Hamiltonian electrostatic coupling scheme for hybrid Car–Parrinello molecular dynamics simulations. J Chem Phys 116(16):6941–6947. https://doi.org/10.1063/1.1462041
doi: 10.1063/1.1462041
Leano JB, Batarni S, Eriksen J, Juge N, Pak JE, Kimura-Someya T, Robles-Colmenares Y, Moriyama Y, Stroud RM, Edwards RH (2019) Structures suggest a mechanism for energy coupling by a family of organic anion transporters. PLoS Biol 17(5):e3000260. https://doi.org/10.1371/journal.pbio.3000260
doi: 10.1371/journal.pbio.3000260
pubmed: 31083648
pmcid: 6532931
Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37(2):785–789. https://doi.org/10.1103/PhysRevB.37.785
doi: 10.1103/PhysRevB.37.785
Li C, Voth GA (2021a) A quantitative paradigm for water-assisted proton transport through proteins and other confined spaces. Proc Natl Acad Sci USA 118(49):e2113141118. https://doi.org/10.1073/pnas.2113141118
doi: 10.1073/pnas.2113141118
pubmed: 34857630
pmcid: 8670507
Li C, Voth GA (2021b) Using constrained density functional theory to track proton transfers and to sample their associated free energy surface. J Chem Theory Comput 17(9):5759–5765. https://doi.org/10.1021/acs.jctc.1c00609
doi: 10.1021/acs.jctc.1c00609
pubmed: 34468142
pmcid: 8444337
Li C, Yue Z, Newstead S, Voth GA (2022) Proton coupling and the multiscale kinetic mechanism of a peptide transporter. Biophys J 121(12):2266–2278. https://doi.org/10.1016/j.bpj.2022.05.029
doi: 10.1016/j.bpj.2022.05.029
pubmed: 35614850
pmcid: 9279349
Li F, Eriksen J, Finer-Moore J, Chang R, Nguyen P, Bowen A, Myasnikov A, Yu Z, Bulkley D, Cheng Y et al (2020) Ion transport and regulation in a synaptic vesicle glutamate transporter. Science 368(6493):893–897. https://doi.org/10.1126/science.aba9202
doi: 10.1126/science.aba9202
pubmed: 32439795
pmcid: 7388591
Li F, Eriksen J, Finer-Moore J, Stroud RM, Edwards RH (2022) Diversity of function and mechanism in a family of organic anion transporters. Curr Opin Struct Biol 75:102399. https://doi.org/10.1016/j.sbi.2022.102399
doi: 10.1016/j.sbi.2022.102399
pubmed: 35660266
pmcid: 9884543
Liu Y, Li C, Gupta M, Stroud RM, Voth GA (2024) Kinetic network modeling with molecular simulation inputs: a proton-coupled phosphate symporter. Biophys J. https://doi.org/10.1016/j.bpj.2024.03.035
Liu Y, Li C, Gupta M, Verma N, Johri AK, Stroud RM, Voth GA (2021) Key computational findings reveal proton transfer as driving the functional cycle in the phosphate transporter PiPT. Proc Natl Acad Sci USA 118(25):e2101932118. https://doi.org/10.1073/pnas.2101932118
doi: 10.1073/pnas.2101932118
pubmed: 34135124
pmcid: 8237618
Lomize MA, Pogozheva ID, Joo H, Mosberg HI, Lomize AL (2012) OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res 40(Database issue):D370–376. https://doi.org/10.1093/nar/gkr703
doi: 10.1093/nar/gkr703
pubmed: 21890895
Madej MG, Sun L, Yan N, Kaback HR (2014) Functional architecture of MFS D-glucose transporters. Proc Natl Acad Sci USA 111(7):E719–727. https://doi.org/10.1073/pnas.1400336111
doi: 10.1073/pnas.1400336111
pubmed: 24550316
pmcid: 3932877
Mangiatordi GF, Brémond E, Adamo C (2012) DFT and proton transfer reactions: a benchmark study on structure and kinetics. J Chem Theory Comput 8(9):3082–3088. https://doi.org/10.1021/ct300338y
doi: 10.1021/ct300338y
pubmed: 26605719
Martyna GJ, Tuckerman ME (1999) A reciprocal space based method for treating long range interactions in ab initio and force-field-based calculations in clusters. J Chem Phys 110(6):2810–2821. https://doi.org/10.1063/1.477923
doi: 10.1063/1.477923
Morin P, Sagné C, Gasnier B (2004) Functional characterization of wild-type and mutant human sialin. EMBO J 23(23):4560–4570. https://doi.org/10.1038/sj.emboj.7600464
doi: 10.1038/sj.emboj.7600464
pubmed: 15510212
pmcid: 533050
Nosé S (1984) A unified formulation of the constant temperature molecular dynamics methods. J Chem Phys 81(1):511–519. https://doi.org/10.1063/1.447334
doi: 10.1063/1.447334
Olsen JMH, Bolnykh V, Meloni S, Ippoliti E, Bircher MP, Carloni P, Rothlisberger U (2019) MiMiC: a novel framework for multiscale modeling in computational chemistry. J Chem Theory Comput 15(6):3810–3823. https://doi.org/10.1021/acs.jctc.9b00093
doi: 10.1021/acs.jctc.9b00093
pubmed: 30998344
Olsson MHM, Søndergaard CR, Rostkowski M, Jensen JH (2011) PROPKA3: consistent treatment of internal and surface residues in empirical p K
doi: 10.1021/ct100578z
pubmed: 26596171
Omote H, Miyaji T, Hiasa M, Juge N, Moriyama Y (2016) Structure, function, and drug interactions of neurotransmitter transporters in the postgenomic era. Annu Rev Pharmacol Toxicol 56:385–402. https://doi.org/10.1146/annurev-pharmtox-010814-124816
doi: 10.1146/annurev-pharmtox-010814-124816
pubmed: 26514205
Parker JL, Li C, Brinth A, Wang Z, Vogeley L, Solcan N, Ledderboge-Vucinic G, Swanson JMJ, Caffrey M, Voth GA, Newstead S (2017) Proton movement and coupling in the POT family of peptide transporters. Proc Natl Acad Sci USA 114(50):13182–13187. https://doi.org/10.1073/pnas.1710727114
doi: 10.1073/pnas.1710727114
pubmed: 29180426
pmcid: 5740623
Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52(12):7182–7190. https://doi.org/10.1063/1.328693
doi: 10.1063/1.328693
Peng Y, Swanson JMJ, Kang S, Zhou R, Voth GA (2015) Hydrated excess protons can create their own water wires. J Phys Chem B 119(29):9212–9218. https://doi.org/10.1021/jp5095118
doi: 10.1021/jp5095118
pubmed: 25369445
Preobraschenski J, Cheret C, Ganzella M, Zander JF, Richter K, Schenck S, Jahn R, Ahnert-Hilger G (2018) Dual and direction-selective mechanisms of phosphate transport by the vesicular glutamate transporter. Cell Rep 23(2):535–545. https://doi.org/10.1016/j.celrep.2018.03.055
doi: 10.1016/j.celrep.2018.03.055
pubmed: 29642010
Quistgaard EM, Löw C, Guettou F, Nordlund P (2016) Understanding transport by the major facilitator superfamily (MFS): structures pave the way. Nat Rev Mol Cell Biol 17(2):123–132. https://doi.org/10.1038/nrm.2015.25
doi: 10.1038/nrm.2015.25
pubmed: 26758938
Qureshi AA, Suades A, Matsuoka R, Brock J, McComas SE, Nji E, Orellana L, Claesson M, Delemotte L, Drew D (2020) The molecular basis for sugar import in malaria parasites. Nature. 578(7794):321–325. https://doi.org/10.1038/s41586-020-1963-z
doi: 10.1038/s41586-020-1963-z
pubmed: 31996846
Raghavan B, Schackert FK, Levy A, Johnson SK, Ippoliti E, Mandelli D, Olsen JMH, Rothlisberger U, Carloni P (2023) MiMiCPy: an efficient toolkit for MiMiC-based QM/MM simulations. J Chem Inf Model 63(5):1406–1412. https://doi.org/10.1021/acs.jcim.2c01620
doi: 10.1021/acs.jcim.2c01620
pubmed: 36811959
pmcid: 10015468
Reimer RJ (2013) SLC17: a functionally diverse family of organic anion transporters. Mol Aspects Med 34(2–3):350–359. https://doi.org/10.1016/j.mam.2012.05.004
doi: 10.1016/j.mam.2012.05.004
pubmed: 23506876
pmcid: 3927456
Scherer MK, Trendelkamp-Schroer B, Paul F, Pérez-Hernández G, Hoffmann M, Plattner N, Wehmeyer C, Prinz J-H, Noé F (2015) PyEMMA 2: a software package for estimation, validation, and analysis of Markov models. J Chem Theory Comput 11(11):5525–5542. https://doi.org/10.1021/acs.jctc.5b00743
doi: 10.1021/acs.jctc.5b00743
pubmed: 26574340
Schrödinger, LLC (2015) The PyMOL Molecular Graphics System, Version 1.8.
Schulz P, Garcia-Celma JJ, Fendler K (2008) SSM-based electrophysiology. Methods 46(2):97–103. https://doi.org/10.1016/j.ymeth.2008.07.002
doi: 10.1016/j.ymeth.2008.07.002
pubmed: 18675360
Slonczewski JL, Rosen BP, Alger JR, Macnab RM (1981) pH homeostasis in Escherichia coli: measurement by
doi: 10.1073/pnas.78.10.6271
pubmed: 7031646
pmcid: 349020
Smirnova I, Kasho V, Kaback HR (2014) Real-time conformational changes in LacY. Proc Natl Acad Sci USA 111(23):8440–8445. https://doi.org/10.1073/pnas.1408374111
doi: 10.1073/pnas.1408374111
pubmed: 24872451
pmcid: 4060661
Smirnova IN, Kasho VN, Kaback HR (2006) Direct sugar binding to LacY measured by resonance energy transfer. Biochemistry 45(51):15279–15287. https://doi.org/10.1021/bi061632m
doi: 10.1021/bi061632m
pubmed: 17176050
Soskine M, Adam Y, Schuldiner S (2004) Direct evidence for substrate-induced proton release in detergent-solubilized EmrE, a multidrug transporter. J Biol Chem 279(11):9951–9955. https://doi.org/10.1074/jbc.M312853200
doi: 10.1074/jbc.M312853200
pubmed: 14701800
Sprik M (2000) Computation of the pK of liquid water using coordination constraints. Chem Phys 258(2):139–150. https://doi.org/10.1016/S0301-0104(00)00129-4
doi: 10.1016/S0301-0104(00)00129-4
Swanson JM (2022) Multiscale kinetic analysis of proteins. Curr Opin Struct Biol 72:169–175. https://doi.org/10.1016/j.sbi.2021.11.005
doi: 10.1016/j.sbi.2021.11.005
pubmed: 34923310
Thomas NE, Feng W, Henzler-Wildman KA (2021) A solid-supported membrane electrophysiology assay for efficient characterization of ion-coupled transport. J Biol Chem 297(4):101220. https://doi.org/10.1016/j.jbc.2021.101220
doi: 10.1016/j.jbc.2021.101220
pubmed: 34562455
pmcid: 8517846
Tiwary P, Parrinello M (2015) A time-independent free energy estimator for metadynamics. J Phys Chem B 119(3):736–742. https://doi.org/10.1021/jp504920s
doi: 10.1021/jp504920s
pubmed: 25046020
Tribello GA, Bonomi M, Branduardi D, Camilloni C, Bussi G (2014) PLUMED 2: new feathers for an old bird. Comput Phys Commun 185(2):604–613. https://doi.org/10.1016/j.cpc.2013.09.018
doi: 10.1016/j.cpc.2013.09.018
Troullier N, Martins JL (1991) Efficient pseudopotentials for plane-wave calculations. Phys Rev B 43(3):1993–2006. https://doi.org/10.1103/physrevb.43.1993
doi: 10.1103/physrevb.43.1993
von Lilienfeld OA, Tavernelli I, Rothlisberger U, Sebastiani D (2005) Variational optimization of effective atom centered potentials for molecular properties. J Chem Phys 122(1):14113. https://doi.org/10.1063/1.1829051
doi: 10.1063/1.1829051
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L et al (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46(W1):W296–W303. https://doi.org/10.1093/nar/gky427
doi: 10.1093/nar/gky427
pubmed: 29788355
pmcid: 6030848
Wolf MG, Hoefling M, Aponte-Santamaría C, Grubmüller H, Groenhof G (2010) g_membed: efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation. J Comput Chem 31(11):2169–2174. https://doi.org/10.1002/jcc.21507
doi: 10.1002/jcc.21507
pubmed: 20336801
Yamamura R, Inoue KY, Nishino K, Yamasaki S (2023) Intestinal and fecal pH in human health. Front Microbiomes 2:1192316. https://doi.org/10.3389/frmbi.2023.1192316
Zoete V, Cuendet MA, Grosdidier A, Michielin O (2011) SwissParam: a fast force field generation tool for small organic molecules. J Comput Chem 32(11):2359–2368. https://doi.org/10.1002/jcc.21816
doi: 10.1002/jcc.21816
pubmed: 21541964