John Louis Medabalimi, Ph.D. (alias: John M. Louis)

Research Biologist: Laboratory of Chemical Physics
Scientific Focus Areas: Chemical Biology, Molecular Biology and Biochemistry, Structural Biology


A selection of recent and significant publications can be viewed below.

Three-Color Single-Molecule FRET and Fluorescence Lifetime Analysis of Fast Protein Folding.
Yoo J, Louis JM, Gopich IV, Chung HS.
J Phys Chem B (2018 Oct 10) Abstract/Full Text
Co-Evolutionary Fitness Landscapes for Sequence Design.
Tian P, Louis JM, Baber JL, Aniana A, Best RB.
Angew Chem Int Ed Engl (2018 May 14) 57:5674-5678. Abstract/Full Text
Binding kinetics and substrate selectivity in HIV-1 protease-Gag interactions probed at atomic resolution by chemical exchange NMR.
Deshmukh L, Tugarinov V, Louis JM, Clore GM.
Proc Natl Acad Sci U S A (2017 Nov 14) 114:E9855-E9862. Abstract/Full Text
Oligomerization of the tetramerization domain of p53 probed by two- and three-color single-molecule FRET.
Chung HS, Meng F, Kim JY, McHale K, Gopich IV, Louis JM.
Proc Natl Acad Sci U S A (2017 Aug 15) 114:E6812-E6821. Abstract/Full Text
Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations.
Deshmukh L, Louis JM, Ghirlando R, Clore GM.
Proc Natl Acad Sci U S A (2016 Nov 1) 113:12456-12461. Abstract/Full Text
Insights into the Conformation of the Membrane Proximal Regions Critical to the Trimerization of the HIV-1 gp41 Ectodomain Bound to Dodecyl Phosphocholine Micelles.
Louis JM, Baber JL, Ghirlando R, Aniana A, Bax A, Roche J.
PLoS One (2016) 11:e0160597. Abstract/Full Text
Evolution under Drug Pressure Remodels the Folding Free-Energy Landscape of Mature HIV-1 Protease.
Louis JM, Roche J.
J Mol Biol (2016 Jul 3) 428:2780-92. Abstract/Full Text
Binding of Clinical Inhibitors to a Model Precursor of a Rationally Selected Multidrug Resistant HIV-1 Protease Is Significantly Weaker Than That to the Released Mature Enzyme.
Park JH, Sayer JM, Aniana A, Yu X, Weber IT, Harrison RW, Louis JM.
Biochemistry (2016 Apr 26) 55:2390-400. Abstract/Full Text
The C34 Peptide Fusion Inhibitor Binds to the Six-Helix Bundle Core Domain of HIV-1 gp41 by Displacement of the C-Terminal Helical Repeat Region.
Louis JM, Baber JL, Clore GM.
Biochemistry (2015 Nov 17) 54:6796-805. Abstract/Full Text
Dependence of distance distributions derived from double electron-electron resonance pulsed EPR spectroscopy on pulse-sequence time.
Baber JL, Louis JM, Clore GM.
Angew Chem Int Ed Engl (2015 Apr 27) 54:5336-9. Abstract/Full Text
Conformation of inhibitor-free HIV-1 protease derived from NMR spectroscopy in a weakly oriented solution.
Roche J, Louis JM, Bax A.
Chembiochem (2015 Jan 19) 16:214-8. Abstract/Full Text
Binding of HIV-1 gp41-directed neutralizing and non-neutralizing fragment antibody binding domain (Fab) and single chain variable fragment (ScFv) antibodies to the ectodomain of gp41 in the pre-hairpin and six-helix bundle conformations.
Louis JM, Aniana A, Lohith K, Sayer JM, Roche J, Bewley CA, Clore GM.
PLoS One (2014) 9:e104683. Abstract/Full Text
Dissociation of the trimeric gp41 ectodomain at the lipid-water interface suggests an active role in HIV-1 Env-mediated membrane fusion.
Roche J, Louis JM, Grishaev A, Ying J, Bax A.
Proc Natl Acad Sci U S A (2014 Mar 4) 111:3425-30. Abstract/Full Text
Mechanism of dissociative inhibition of HIV protease and its autoprocessing from a precursor.
Sayer JM, Aniana A, Louis JM.
J Mol Biol (2012 Sep 14) 422:230-44. Abstract/Full Text
HIV-1 protease with 20 mutations exhibits extreme resistance to clinical inhibitors through coordinated structural rearrangements.
Agniswamy J, Shen CH, Aniana A, Sayer JM, Louis JM, Weber IT.
Biochemistry (2012 Apr 3) 51:2819-28. Abstract/Full Text
Single-molecule fluorescence experiments determine protein folding transition path times.
Chung HS, McHale K, Louis JM, Eaton WA.
Science (2012 Feb 24) 335:981-4. Abstract/Full Text
Terminal interface conformations modulate dimer stability prior to amino terminal autoprocessing of HIV-1 protease.
Agniswamy J, Sayer JM, Weber IT, Louis JM.
Biochemistry (2012 Feb 7) 51:1041-50. Abstract/Full Text
Evolution of cyclic peptide protease inhibitors.
Young TS, Young DD, Ahmad I, Louis JM, Benkovic SJ, Schultz PG.
Proc Natl Acad Sci U S A (2011 Jul 5) 108:11052-6. Abstract/Full Text
Inhibition of autoprocessing of natural variants and multidrug resistant mutant precursors of HIV-1 protease by clinical inhibitors.
Louis JM, Aniana A, Weber IT, Sayer JM.
Proc Natl Acad Sci U S A (2011 May 31) 108:9072-7. Abstract/Full Text
The complete influenza hemagglutinin fusion domain adopts a tight helical hairpin arrangement at the lipid:water interface.
Lorieau JL, Louis JM, Bax A.
Proc Natl Acad Sci U S A (2010 Jun 22) 107:11341-6. Abstract/Full Text
Highly conserved glycine 86 and arginine 87 residues contribute differently to the structure and activity of the mature HIV-1 protease.
Ishima R, Gong Q, Tie Y, Weber IT, Louis JM.
Proteins (2010 Mar) 78:1015-25. Abstract/Full Text
Experimental determination of upper bound for transition path times in protein folding from single-molecule photon-by-photon trajectories.
Chung HS, Louis JM, Eaton WA.
Proc Natl Acad Sci U S A (2009 Jul 21) 106:11837-44. Abstract/Full Text
Visualizing transient events in amino-terminal autoprocessing of HIV-1 protease.
Tang C, Louis JM, Aniana A, Suh JY, Clore GM.
Nature (2008 Oct 2) 455:693-6. Abstract/Full Text
Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease.
Sayer JM, Liu F, Ishima R, Weber IT, Louis JM.
J Biol Chem (2008 May 9) 283:13459-70. Abstract/Full Text
A diverse view of protein dynamics from NMR studies of HIV-1 protease flaps.
Ishima R, Louis JM.
Proteins (2008 Mar) 70:1408-15. Abstract/Full Text
Caught in the Act: the 1.5 A resolution crystal structures of the HIV-1 protease and the I54V mutant reveal a tetrahedral reaction intermediate.
Kovalevsky AY, Chumanevich AA, Liu F, Louis JM, Weber IT.
Biochemistry (2007 Dec 25) 46:14854-64. Abstract/Full Text
Characterizing the unfolded states of proteins using single-molecule FRET spectroscopy and molecular simulations.
Merchant KA, Best RB, Louis JM, Gopich IV, Eaton WA.
Proc Natl Acad Sci U S A (2007 Jan 30) 104:1528-33. Abstract/Full Text
HIV-1 protease: structure, dynamics, and inhibition.
Louis JM, Ishima R, Torchia DA, Weber IT.
Adv Pharmacol (2007) 55:261-98. Abstract/Full Text
NMR study of the tetrameric KcsA potassium channel in detergent micelles.
Chill JH, Louis JM, Miller C, Bax A.
Protein Sci (2006 Apr) 15:684-98. Abstract/Full Text
The GB1 amyloid fibril: recruitment of the peripheral beta-strands of the domain swapped dimer into the polymeric interface.
Louis JM, Byeon IJ, Baxa U, Gronenborn AM.
J Mol Biol (2005 May 6) 348:687-98. Abstract/Full Text
High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strains.
Tie Y, Boross PI, Wang YF, Gaddis L, Hussain AK, Leshchenko S, Ghosh AK, Louis JM, Harrison RW, Weber IT.
J Mol Biol (2004 Apr 23) 338:341-52. Abstract/Full Text
Insights into conformation and dynamics of protein GB1 during folding and unfolding by NMR.
Ding K, Louis JM, Gronenborn AM.
J Mol Biol (2004 Jan 30) 335:1299-307. Abstract/Full Text
Solution structure of the mature HIV-1 protease monomer: insight into the tertiary fold and stability of a precursor.
Ishima R, Torchia DA, Lynch SM, Gronenborn AM, Louis JM.
J Biol Chem (2003 Oct 31) 278:43311-9. Abstract/Full Text
A protein contortionist: core mutations of GB1 that induce dimerization and domain swapping.
Byeon IJ, Louis JM, Gronenborn AM.
J Mol Biol (2003 Oct 10) 333:141-52. Abstract/Full Text
A solution NMR study of the binding kinetics and the internal dynamics of an HIV-1 protease-substrate complex.
Katoh E, Louis JM, Yamazaki T, Gronenborn AM, Torchia DA, Ishima R.
Protein Sci (2003 Jul) 12:1376-85. Abstract/Full Text
Covalent trimers of the internal N-terminal trimeric coiled-coil of gp41 and antibodies directed against them are potent inhibitors of HIV envelope-mediated cell fusion.
Louis JM, Nesheiwat I, Chang L, Clore GM, Bewley CA.
J Biol Chem (2003 May 30) 278:20278-85. Abstract/Full Text
The structure of a replication initiator unites diverse aspects of nucleic acid metabolism.
Campos-Olivas R, Louis JM, Clerot D, Gronenborn B, Gronenborn AM.
Proc Natl Acad Sci U S A (2002 Aug 6) 99:10310-5. Abstract/Full Text
Design of a novel peptide inhibitor of HIV fusion that disrupts the internal trimeric coiled-coil of gp41.
Bewley CA, Louis JM, Ghirlando R, Clore GM.
J Biol Chem (2002 Apr 19) 277:14238-45. Abstract/Full Text
Structure and dynamics of KH domains from FBP bound to single-stranded DNA.
Braddock DT, Louis JM, Baber JL, Levens D, Clore GM.
Nature (2002 Feb 28) 415:1051-6. Abstract/Full Text
Rapid structural fluctuations of the free HIV protease flaps in solution: relationship to crystal structures and comparison with predictions of dynamics calculations.
Freedberg DI, Ishima R, Jacob J, Wang YX, Kustanovich I, Louis JM, Torchia DA.
Protein Sci (2002 Feb) 11:221-32. Abstract/Full Text
Folded monomer of HIV-1 protease.
Ishima R, Ghirlando R, Tözsér J, Gronenborn AM, Torchia DA, Louis JM.
J Biol Chem (2001 Dec 28) 276:49110-6. Abstract/Full Text
A simple apparatus for generating stretched polyacrylamide gels, yielding uniform alignment of proteins and detergent micelles.
Chou JJ, Gaemers S, Howder B, Louis JM, Bax A.
J Biomol NMR (2001 Dec) 21:377-82. Abstract/Full Text
Design and properties of N(CCG)-gp41, a chimeric gp41 molecule with nanomolar HIV fusion inhibitory activity.
Louis JM, Bewley CA, Clore GM.
J Biol Chem (2001 Aug 3) 276:29485-9. Abstract/Full Text
Flap opening and dimer-interface flexibility in the free and inhibitor-bound HIV protease, and their implications for function.
Ishima R, Freedberg DI, Wang YX, Louis JM, Torchia DA.
Structure (1999 Sep 15) 7:1047-55. Abstract/Full Text
Autoprocessing of HIV-1 protease is tightly coupled to protein folding.
Louis JM, Clore GM, Gronenborn AM.
Nat Struct Biol (1999 Sep) 6:868-75. Abstract/Full Text
Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease.
Louis JM, Dyda F, Nashed NT, Kimmel AR, Davies DR.
Biochemistry (1998 Feb 24) 37:2105-10. Abstract/Full Text
Preparation of uniformly isotope-labeled DNA oligonucleotides for NMR spectroscopy.
Louis JM, Martin RG, Clore GM, Gronenborn AM.
J Biol Chem (1998 Jan 23) 273:2374-8. Abstract/Full Text
Kinetics and mechanism of autoprocessing of human immunodeficiency virus type 1 protease from an analog of the Gag-Pol polyprotein.
Louis JM, Nashed NT, Parris KD, Kimmel AR, Jerina DM.
Proc Natl Acad Sci U S A (1994 Aug 16) 91:7970-4. Abstract/Full Text
Chemical synthesis and expression of the HIV-1 protease gene in E. coli.
Louis JM, Wondrak EM, Copeland TD, Smith CA, Mora PT, Oroszlan S.
Biochem Biophys Res Commun (1989 Feb 28) 159:87-94. Abstract/Full Text