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Title: Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface

Abstract

Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.

Authors:
 [1];  [1];  [2];  [3];  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  2. Goethe Univ., Frankfurt (Germany). Inst. of Biochemistry. Cluster of Excellence Frankfurt
  3. Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of Oklahoma, Norman, OK (United States); Goethe Univ., Frankfurt (Germany)
Sponsoring Org.:
USDOE; LANL Laboratory Directed Research and Development (LDRD) Program; Defense Threat Reduction Agency (DTRA) (United States); National Inst. of Health (NIH) (United States); German Research Foundation (DFG); Human Frontier Science Program (HFSP)
OSTI Identifier:
1440470
Report Number(s):
LA-UR-16-27246
Journal ID: ISSN 2045-2322
Grant/Contract Number:  
AC52-06NA25396; HDTRA1-14-1-0019; AI052293; SFB807; EXC115; HFSP-RGP0034/2013
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., and Gnanakaran, S. Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface. United States: N. p., 2017. Web. doi:10.1038/s41598-017-16497-w.
Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., & Gnanakaran, S. Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface. United States. doi:10.1038/s41598-017-16497-w.
Lopez, Cesar A., Travers, Timothy, Pos, Klaas M., Zgurskaya, Helen I., and Gnanakaran, S. Tue . "Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface". United States. doi:10.1038/s41598-017-16497-w. https://www.osti.gov/servlets/purl/1440470.
@article{osti_1440470,
title = {Dynamics of Intact MexAB-OprM Efflux Pump: Focusing on the MexA-OprM Interface},
author = {Lopez, Cesar A. and Travers, Timothy and Pos, Klaas M. and Zgurskaya, Helen I. and Gnanakaran, S.},
abstractNote = {Antibiotic efflux is one of the most critical mechanisms leading to bacterial multidrug resistance. Antibiotics are effluxed out of the bacterial cell by a tripartite efflux pump, a complex machinery comprised of outer membrane, periplasmic adaptor, and inner membrane protein components. Understanding the mechanism of efflux pump assembly and its dynamics could facilitate discovery of novel approaches to counteract antibiotic resistance in bacteria. We built here an intact atomistic model of the Pseudomonas aeruginosa MexAB-OprM pump in a Gram-negative membrane model that contained both inner and outer membranes separated by a periplasmic space. All-atom molecular dynamics (MD) simulations confirm that the fully assembled pump is stable in the microsecond timescale. Using a combination of all-atom and coarse-grained MD simulations and sequence covariation analysis, we characterized the interface between MexA and OprM in the context of the entire efflux pump. These analyses suggest a plausible mechanism by which OprM is activated via opening of its periplasmic aperture through a concerted interaction with MexA.},
doi = {10.1038/s41598-017-16497-w},
journal = {Scientific Reports},
issn = {2045-2322},
number = ,
volume = 7,
place = {United States},
year = {2017},
month = {11}
}

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Works referenced in this record:

Nonphysical sampling distributions in Monte Carlo free-energy estimation: Umbrella sampling
journal, February 1977


Assembly and Channel Opening in a Bacterial Drug Efflux Machine
journal, April 2008


Structure of the AcrAB–TolC multidrug efflux pump
journal, April 2014

  • Du, Dijun; Wang, Zhao; James, Nathan R.
  • Nature, Vol. 509, Issue 7501
  • DOI: 10.1038/nature13205

Tripartite assembly of RND multidrug efflux pumps
journal, February 2016

  • Daury, Laetitia; Orange, François; Taveau, Jean-Christophe
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms10731

The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa
journal, June 2014

  • Terzi, Huseyin Agah; Kulah, Canan; Ciftci, İhsan Hakkı
  • World Journal of Microbiology and Biotechnology, Vol. 30, Issue 10
  • DOI: 10.1007/s11274-014-1692-2

Comparison of simple potential functions for simulating liquid water
journal, July 1983

  • Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D.
  • The Journal of Chemical Physics, Vol. 79, Issue 2
  • DOI: 10.1063/1.445869

Breaking the Spell: Combating Multidrug Resistant ‘Superbugs’
journal, February 2016


Bacterial Multidrug Efflux Transporters
journal, May 2014


Crystal structure of bacterial multidrug efflux transporter AcrB
journal, October 2002

  • Murakami, Satoshi; Nakashima, Ryosuke; Yamashita, Eiki
  • Nature, Vol. 419, Issue 6907
  • DOI: 10.1038/nature01050

Keep It Flexible: Driving Macromolecular Rotary Motions in Atomistic Simulations with GROMACS
journal, March 2011

  • Kutzner, Carsten; Czub, Jacek; Grubmüller, Helmut
  • Journal of Chemical Theory and Computation, Vol. 7, Issue 5
  • DOI: 10.1021/ct100666v

The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria
journal, March 2015

  • Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi
  • Clinical Microbiology Reviews, Vol. 28, Issue 2
  • DOI: 10.1128/CMR.00117-14

Lipid14: The Amber Lipid Force Field
journal, January 2014

  • Dickson, Callum J.; Madej, Benjamin D.; Skjevik, Åge A.
  • Journal of Chemical Theory and Computation, Vol. 10, Issue 2
  • DOI: 10.1021/ct4010307

Crystal Structure of the Periplasmic Component of a Tripartite Macrolide-Specific Efflux Pump
journal, April 2009


Structure of the periplasmic component of a bacterial drug efflux pump
journal, June 2004

  • Higgins, M. K.; Bokma, E.; Koronakis, E.
  • Proceedings of the National Academy of Sciences, Vol. 101, Issue 27
  • DOI: 10.1073/pnas.0400375101

Structure of the MacAB–TolC ABC-type tripartite multidrug efflux pump
journal, May 2017

  • Fitzpatrick, Anthony W. P.; Llabrés, Salomé; Neuberger, Arthur
  • Nature Microbiology, Vol. 2, Issue 7
  • DOI: 10.1038/nmicrobiol.2017.70

Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa
journal, September 2000


Interactions underlying assembly of the Escherichia coli AcrAB-TolC multidrug efflux system: Multidrug efflux system assembly
journal, June 2004


LAMBADA and InflateGRO2: Efficient Membrane Alignment and Insertion of Membrane Proteins for Molecular Dynamics Simulations
journal, September 2012

  • Schmidt, Thomas H.; Kandt, Christian
  • Journal of Chemical Information and Modeling, Vol. 52, Issue 10
  • DOI: 10.1021/ci3000453

Mutations in MexB that affect the efflux of antibiotics with cytoplasmic targets
journal, May 2012


An allosteric transport mechanism for the AcrAB-TolC multidrug efflux pump
journal, March 2017


The assembly and disassembly of the AcrAB-TolC three-component multidrug efflux pump
journal, September 2015

  • Müller, Reinke Tobias; Pos, Klaas Martinus
  • Biological Chemistry, Vol. 396, Issue 9-10
  • DOI: 10.1515/hsz-2015-0150

Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections
journal, February 2016


Crystal Structure of the Multidrug Exporter MexB from Pseudomonas aeruginosa
journal, May 2009

  • Sennhauser, Gaby; Bukowska, Magdalena A.; Briand, Christophe
  • Journal of Molecular Biology, Vol. 389, Issue 1
  • DOI: 10.1016/j.jmb.2009.04.001

Canonical sampling through velocity rescaling
journal, January 2007

  • Bussi, Giovanni; Donadio, Davide; Parrinello, Michele
  • The Journal of Chemical Physics, Vol. 126, Issue 1
  • DOI: 10.1063/1.2408420

Within-host evolution of bacterial pathogens
journal, January 2016

  • Didelot, Xavier; Walker, A. Sarah; Peto, Tim E.
  • Nature Reviews Microbiology, Vol. 14, Issue 3
  • DOI: 10.1038/nrmicro.2015.13

Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems
journal, June 1993

  • Darden, Tom; York, Darrin; Pedersen, Lee
  • The Journal of Chemical Physics, Vol. 98, Issue 12
  • DOI: 10.1063/1.464397

Drug export and allosteric coupling in a multidrug transporter revealed by molecular simulations
journal, November 2010

  • Yao, Xin-Qiu; Kenzaki, Hiroo; Murakami, Satoshi
  • Nature Communications, Vol. 1, Issue 1
  • DOI: 10.1038/ncomms1116

Molecular dynamics with coupling to an external bath
journal, October 1984

  • Berendsen, H. J. C.; Postma, J. P. M.; van Gunsteren, W. F.
  • The Journal of Chemical Physics, Vol. 81, Issue 8
  • DOI: 10.1063/1.448118

Mechanism of coupling drug transport reactions located in two different membranes
journal, February 2015


Polarizable Water Model for the Coarse-Grained MARTINI Force Field
journal, June 2010


Opening the Channel: the Two Functional Interfaces of Pseudomonas aeruginosa OpmH with the Triclosan Efflux Pump TriABC
journal, September 2016

  • Ntreh, Abigail T.; Weeks, Jon W.; Nickels, Logan M.
  • Journal of Bacteriology, Vol. 198, Issue 23
  • DOI: 10.1128/jb.00535-16

Flexibility in a Drug Transport Accessory Protein: Molecular Dynamics Simulations of MexA
journal, July 2006


Multidrug efflux transporter, AcrB—the pumping mechanism
journal, August 2008


Fitting Periplasmic Membrane Fusion Proteins to Inner Membrane Transporters: Mutations That Enable Escherichia coli AcrA To Function with Pseudomonas aeruginosa MexB
journal, November 2007

  • Krishnamoorthy, G.; Tikhonova, E. B.; Zgurskaya, H. I.
  • Journal of Bacteriology, Vol. 190, Issue 2
  • DOI: 10.1128/JB.01276-07

Escherichia coli Peptidoglycan Structure and Mechanics as Predicted by Atomic-Scale Simulations
journal, February 2014


Structure and Function of TolC: The Bacterial Exit Duct for Proteins and Drugs
journal, June 2004


g_wham—A Free Weighted Histogram Analysis Implementation Including Robust Error and Autocorrelation Estimates
journal, November 2010

  • Hub, Jochen S.; de Groot, Bert L.; van der Spoel, David
  • Journal of Chemical Theory and Computation, Vol. 6, Issue 12
  • DOI: 10.1021/ct100494z

Understanding the mechanisms and drivers of antimicrobial resistance
journal, January 2016


Advances in the molecular dynamics flexible fitting method for cryo-EM modeling
journal, May 2016


Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli
journal, February 2011

  • Su, Chih-Chia; Long, Feng; Zimmermann, Michael T.
  • Nature, Vol. 470, Issue 7335
  • DOI: 10.1038/nature09743

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps
journal, July 2016


Decreased outer membrane permeability in imipenem-resistant mutants of Pseudomonas aeruginosa.
journal, August 1989

  • Trias, J.; Dufresne, J.; Levesque, R. C.
  • Antimicrobial Agents and Chemotherapy, Vol. 33, Issue 8
  • DOI: 10.1128/AAC.33.8.1202

Pseudomonas aeruginosa – a phenomenon of bacterial resistance
journal, September 2009

  • Yordanov, Daniel; Strateva, Tanya
  • Journal of Medical Microbiology, Vol. 58, Issue 9
  • DOI: 10.1099/jmm.0.009142-0

Mechanistic Parallels in Bacterial and Human Multidrug Efflux Transporters
journal, October 2002


Cryo-Transmission Electron Microscopy of Frozen-Hydrated Sections of Escherichia coli and Pseudomonas aeruginosa
journal, October 2003


An overview of bacterial efflux pumps and computational approaches to study efflux pump inhibitors
journal, February 2016

  • Jamshidi, Shirin; Sutton, J. Mark; Rahman, Khondaker M.
  • Future Medicinal Chemistry, Vol. 8, Issue 2
  • DOI: 10.4155/fmc.15.173

Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance
journal, October 2014

  • Blair, Jessica MA; Richmond, Grace E.; Piddock, Laura JV
  • Future Microbiology, Vol. 9, Issue 10
  • DOI: 10.2217/fmb.14.66

Assembly and Channel Opening of Outer Membrane Protein in Tripartite Drug Efflux Pumps of Gram-negative Bacteria
journal, February 2012

  • Xu, Yongbin; Moeller, Arne; Jun, So-Young
  • Journal of Biological Chemistry, Vol. 287, Issue 15
  • DOI: 10.1074/jbc.M111.329375

Sequence co-evolution gives 3D contacts and structures of protein complexes
journal, September 2014

  • Hopf, Thomas A.; Schärfe, Charlotta P. I.; Rodrigues, João P. G. L. M.
  • eLife, Vol. 3
  • DOI: 10.7554/eLife.03430

Improved side-chain torsion potentials for the Amber ff99SB protein force field
journal, January 2010

  • Lindorff-Larsen, Kresten; Piana, Stefano; Palmo, Kim
  • Proteins: Structure, Function, and Bioinformatics
  • DOI: 10.1002/prot.22711

Structural basis of RND-type multidrug exporters
journal, April 2015

  • Yamaguchi, Akihito; Nakashima, Ryosuke; Sakurai, Keisuke
  • Frontiers in Microbiology, Vol. 6
  • DOI: 10.3389/fmicb.2015.00327

P-LINCS:  A Parallel Linear Constraint Solver for Molecular Simulation
journal, December 2007

  • Hess, Berk
  • Journal of Chemical Theory and Computation, Vol. 4, Issue 1
  • DOI: 10.1021/ct700200b

Crystal Structure of the Drug Discharge Outer Membrane Protein, OprM, of Pseudomonas aeruginosa : DUAL MODES OF MEMBRANE ANCHORING AND OCCLUDED CAVITY END
journal, October 2004

  • Akama, Hiroyuki; Kanemaki, Misa; Yoshimura, Masato
  • Journal of Biological Chemistry, Vol. 279, Issue 51
  • DOI: 10.1074/jbc.C400445200

Computational Methodologies for Real-Space Structural Refinement of Large Macromolecular Complexes
journal, July 2016


GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit
journal, February 2013


Multidrug-Resistant Gram-Negative Bacterial Infections in the Hospital Setting: Overview, Implications for Clinical Practice, and Emerging Treatment Options
journal, July 2016

  • Cerceo, Elizabeth; Deitelzweig, Steven B.; Sherman, Bradley M.
  • Microbial Drug Resistance, Vol. 22, Issue 5
  • DOI: 10.1089/mdr.2015.0220

Isolation and characterization of antibiotic-resistant bacteria from pharmaceutical industrial wastewaters
journal, December 2015


A data-driven approach to modeling the tripartite structure of multidrug resistance efflux pumps: Modeling of Multidrug Resistance Efflux Pumps
journal, November 2014

  • Phillips, Joshua L.; Gnanakaran, S.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 83, Issue 1
  • DOI: 10.1002/prot.24632

Resistance Mechanisms in Pseudomonas aeruginosa and Other Nonfermentative Gram‐Negative Bacteria
journal, August 1998

  • Hancock, Robert E. W.
  • Clinical Infectious Diseases, Vol. 27, Issue s1
  • DOI: 10.1086/514909

RETRACTED ARTICLE: Profile of Virulence Factors in the Multi-Drug Resistant Pseudomonas aeruginosa Strains of Human Urinary Tract Infections (UTI)
journal, December 2015

  • Habibi, Asghar; Honarmand, Ramin
  • Iranian Red Crescent Medical Journal, Vol. 17, Issue 12
  • DOI: 10.5812/ircmj.26095

Antibiotic efflux mechanisms
journal, January 1999


Crystal Structure and Pair Potentials: A Molecular-Dynamics Study
journal, October 1980


Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB
journal, September 2014


Outer membrane permeability and antibiotic resistance
journal, May 2009


Structure, mechanism and cooperation of bacterial multidrug transporters
journal, August 2015

  • Du, Dijun; van Veen, Hendrik W.; Murakami, Satoshi
  • Current Opinion in Structural Biology, Vol. 33
  • DOI: 10.1016/j.sbi.2015.07.015

Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
journal, January 2015

  • Schulz, Robert; Vargiu, Attilio V.; Ruggerone, Paolo
  • BioMed Research International, Vol. 2015
  • DOI: 10.1155/2015/487298

Molecular Dynamics Computer Simulations of Multidrug rnd Efflux Pumps
journal, February 2013

  • Ruggerone, Paolo; Vargiu, Attilio V.; Collu, Francesca
  • Computational and Structural Biotechnology Journal, Vol. 5, Issue 6
  • DOI: 10.5936/csbj.201302008

Antibiotic resistance in Pseudomonas aeruginosa and alternative therapeutic options
journal, January 2016

  • Chatterjee, Maitrayee; Anju, C. P.; Biswas, Lalitha
  • International Journal of Medical Microbiology, Vol. 306, Issue 1
  • DOI: 10.1016/j.ijmm.2015.11.004

Unilateral Access Regulation: Ground State Dynamics of the Pseudomonas aeruginosa Outer Membrane Efflux Duct OprM
journal, December 2012

  • Koch, Dennis C.; Raunest, Martin; Harder, Tim
  • Biochemistry, Vol. 52, Issue 1
  • DOI: 10.1021/bi3014714

Structure of reconstituted bacterial membrane efflux pump by cryo-electron tomography
journal, October 2010

  • Trépout, Sylvain; Taveau, Jean-Christophe; Benabdelhak, Houssain
  • Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 10
  • DOI: 10.1016/j.bbamem.2010.06.019

Residue – Residue Potentials with a Favorable Contact Pair Term and an Unfavorable High Packing Density Term, for Simulation and Threading
journal, March 1996

  • Miyazawa, Sanzo; Jernigan, Robert L.
  • Journal of Molecular Biology, Vol. 256, Issue 3
  • DOI: 10.1006/jmbi.1996.0114

Functional Rotation Induced by Alternating Protonation States in the Multidrug Transporter AcrB: All-Atom Molecular Dynamics Simulations
journal, October 2013

  • Yamane, Tsutomu; Murakami, Satoshi; Ikeguchi, Mitsunori
  • Biochemistry, Vol. 52, Issue 43
  • DOI: 10.1021/bi400119v

Sequential Mechanism of Assembly of Multidrug Efflux Pump AcrAB-TolC
journal, April 2011


AcrA is a highly asymmetric protein capable of spanning the periplasm 1 1Edited by I. B. Holland
journal, January 1999

  • Zgurskaya, Helen I.; Nikaido, Hiroshi
  • Journal of Molecular Biology, Vol. 285, Issue 1
  • DOI: 10.1006/jmbi.1998.2313

Catch me if you can: a biotinylated proteoliposome affinity assay for the investigation of assembly of the MexA-MexB-OprM efflux pump from Pseudomonas aeruginosa
journal, June 2015

  • Ntsogo Enguéné, Véronique Yvette; Verchère, Alice; Phan, Gilles
  • Frontiers in Microbiology, Vol. 6
  • DOI: 10.3389/fmicb.2015.00541

Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa
journal, July 2015


Functional replacement of OprJ by OprM in the MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa
journal, August 1998


Generating stereochemically acceptable protein pathways
journal, September 2010

  • Farrell, Daniel W.; Speranskiy, Kirill; Thorpe, M. F.
  • Proteins: Structure, Function, and Bioinformatics, Vol. 78, Issue 14
  • DOI: 10.1002/prot.22810

Conformational Flexibility in the Multidrug Efflux System Protein AcrA
journal, March 2006


Multidrug Resistant and Extensively Drug Resistant Bacteria: A Study
journal, January 2016

  • Basak, Silpi; Singh, Priyanka; Rajurkar, Monali
  • Journal of Pathogens, Vol. 2016
  • DOI: 10.1155/2016/4065603

Drug Uptake Pathways of Multidrug Transporter AcrB Studied by Molecular Simulations and Site-Directed Mutagenesis Experiments
journal, May 2013

  • Yao, Xin-Qiu; Kimura, Nobuhiro; Murakami, Satoshi
  • Journal of the American Chemical Society, Vol. 135, Issue 20
  • DOI: 10.1021/ja310548h

Molecular Dynamics and NMR Spectroscopy Studies of E. coli Lipopolysaccharide Structure and Dynamics
journal, September 2013


Crystal Structure of the Membrane Fusion Protein, MexA, of the Multidrug Transporter in Pseudomonas aeruginosa
journal, April 2004

  • Akama, Hiroyuki; Matsuura, Takanori; Kashiwagi, Sachiko
  • Journal of Biological Chemistry, Vol. 279, Issue 25
  • DOI: 10.1074/jbc.C400164200

New OprM structure highlighting the nature of the N-terminal anchor
journal, July 2015


Molecular dynamics flexible fitting: A practical guide to combine cryo-electron microscopy and X-ray crystallography
journal, October 2009


Electrophysiological Behavior of the TolC Channel-Tunnel in Planar Lipid Bilayers
journal, January 2002


The MARTINI Force Field:  Coarse Grained Model for Biomolecular Simulations
journal, July 2007

  • Marrink, Siewert J.; Risselada, H. Jelger; Yefimov, Serge
  • The Journal of Physical Chemistry B, Vol. 111, Issue 27
  • DOI: 10.1021/jp071097f

Structures of sequential open states in a symmetrical opening transition of the TolC exit duct
journal, January 2011

  • Pei, Xue-Yuan; Hinchliffe, Philip; Symmons, Martyn F.
  • Proceedings of the National Academy of Sciences, Vol. 108, Issue 5
  • DOI: 10.1073/pnas.1012588108

Robust and accurate prediction of residue–residue interactions across protein interfaces using evolutionary information
journal, May 2014

  • Ovchinnikov, Sergey; Kamisetty, Hetunandan; Baker, David
  • eLife, Vol. 3
  • DOI: 10.7554/eLife.02030

Multiple conformational states and gate opening of outer membrane protein TolC revealed by molecular dynamics simulations: MD Simulation of TolC
journal, June 2014

  • Wang, Beibei; Weng, Jingwei; Wang, Wenning
  • Proteins: Structure, Function, and Bioinformatics, Vol. 82, Issue 9
  • DOI: 10.1002/prot.24573

Structural and Dynamical Insights into the Opening Mechanism of P. aeruginosa OprM Channel
journal, March 2010


Permeability Barrier of Gram-Negative Cell Envelopes and Approaches To Bypass It
journal, August 2015


Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB
journal, February 2015

  • Mishima, Hirokazu; Oshima, Hiraku; Yasuda, Satoshi
  • The Journal of Physical Chemistry B, Vol. 119, Issue 8
  • DOI: 10.1021/jp5120724

Pseudomonas aeruginosa: all roads lead to resistance
journal, August 2011

  • Breidenstein, Elena B. M.; de la Fuente-Núñez, César; Hancock, Robert E. W.
  • Trends in Microbiology, Vol. 19, Issue 8
  • DOI: 10.1016/j.tim.2011.04.005

Ultra-fast FFT protein docking on graphics processors
journal, August 2010