Terry P. Lybrand, Ph.D.



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Faculty Appointments
Professor of Chemistry Professor of Pharmacology
Ph.D., Chemistry, Physical, University of California, San Francisco, CaliforniaB.S., University of South Carolina, Columbia, South Carolina
Office Address
VU Station B 351822
7332 Stevenson Center
Nashville, TN 37235-1822
Research Description
In our laboratory, we utilize computational methods to study the properties and behavior of biomacromolecules and ligand-biomacromolecule complexes, and to aid in the design of small molecule ligands with desired binding properties for targeted receptors. Techniques used include quantum mechanical calculations, molecular dynamics and Monte Carlo simulation, and free energy perturbation methods.

See http://structbio.vanderbilt.edu/lybrand/
Research Keywords
Molecular modeling and computational chemistry
Sárosi MB, Neumann W, Lybrand TP, Hey-Hawkins E. Molecular Modeling of the Interactions between Carborane-Containing Analogs of Indomethacin and Cyclooxygenase-2. J Chem Inf Model [print-electronic]. 2017 Jul 7/21/2017; PMID: 28632381, DOI: 10.1021/acs.jcim.7b00113, ISSN: 1549-960X.

Abeydeera ND, Egli M, Cox N, Mercier K, Conde JN, Pallan PS, Mizurini DM, Sierant M, Hibti FE, Hassell T, Wang T, Liu FW, Liu HM, Martinez C, Sood AK, Lybrand TP, Frydman C, Monteiro RQ, Gomer RH, Nawrot B, Yang X. Evoking picomolar binding in RNA by a single phosphorodithioate linkage. Nucleic Acids Res [print-electronic]. 2016 Sep 9/30/2016; 44(17): 8052-64. PMID: 27566147, PMCID: PMC5041495, PII: gkw725, DOI: 10.1093/nar/gkw725, ISSN: 1362-4962.

Baugh L, Le Trong I, Stayton PS, Stenkamp RE, Lybrand TP. A Streptavidin Binding Site Mutation Yields an Unexpected Result: An Ionized Asp128 Residue Is Not Essential for Strong Biotin Binding. Biochemistry [print-electronic]. 2016 Sep 9/20/2016; 55(37): 5201-3. PMID: 27603565, PMCID: PMC5030189, DOI: 10.1021/acs.biochem.6b00698, ISSN: 1520-4995.

Konkle ME, Blobaum AL, Moth CW, Prusakiewicz JJ, Xu S, Ghebreselasie K, Akingbade D, Jacobs AT, Rouzer CA, Lybrand TP, Marnett LJ. Conservative Secondary Shell Substitution In Cyclooxygenase-2 Reduces Inhibition by Indomethacin Amides and Esters via Altered Enzyme Dynamics. Biochemistry [print-electronic]. 2016 Jan 1/19/2016; 55(2): 348-59. PMID: 26704937, PMCID: PMC4721528, DOI: 10.1021/acs.biochem.5b01222, ISSN: 1520-4995.

Weber DK, Yao S, Rojko N, Anderluh G, Lybrand TP, Downton MT, Wagner J, Separovic F. Characterization of the Lipid-Binding Site of Equinatoxin II by NMR and Molecular Dynamics Simulation. Biophys. J. 2015 Apr 4/21/2015; 108(8): 1987-96. PMID: 25902438, PMCID: PMC4407268, PII: S0006-3495(15)00285-4, DOI: 10.1016/j.bpj.2015.03.024, ISSN: 1542-0086.

Stow SM, Goodwin CR, Kliman M, Bachmann BO, McLean JA, Lybrand TP. Distance geometry protocol to generate conformations of natural products to structurally interpret ion mobility-mass spectrometry collision cross sections. J Phys Chem B [print-electronic]. 2014 Dec 12/4/2014; 118(48): 13812-20. PMID: 25360896, PMCID: PMC4259499, DOI: 10.1021/jp509398e, ISSN: 1520-5207.

Edwards SJ, Moth CW, Kim S, Brandon S, Zhou Z, Cobb CE, Hustedt EJ, Beth AH, Smith JA, Lybrand TP. Automated structure refinement for a protein heterodimer complex using limited EPR spectroscopic data and a rigid-body docking algorithm: a three-dimensional model for an ankyrin-CDB3 complex. J Phys Chem B [print-electronic]. 2014 May 5/8/2014; 118(18): 4717-26. PMID: 24758720, PMCID: PMC4018176, DOI: 10.1021/jp4099705, ISSN: 1520-5207.

Smith JA, Edwards SJ, Moth CW, Lybrand TP. TagDock: an efficient rigid body docking algorithm for oligomeric protein complex model construction and experiment planning. Biochemistry [print-electronic]. 2013 Aug 8/20/2013; 52(33): 5577-84. PMID: 23875708, PMCID: PMC3804560, DOI: 10.1021/bi400158k, ISSN: 1520-4995.

Kim S, Brandon S, Zhou Z, Cobb CE, Edwards SJ, Moth CW, Parry CS, Smith JA, Lybrand TP, Hustedt EJ, Beth AH. Determination of structural models of the complex between the cytoplasmic domain of erythrocyte band 3 and ankyrin-R repeats 13-24. J. Biol. Chem [print-electronic]. 2011 Jun 6/10/2011; 286(23): 20746-57. PMID: 21493712, PMCID: PMC3121456, PII: M111.230326, DOI: 10.1074/jbc.M111.230326, ISSN: 1083-351X.

Cerutti DS, Duke RE, Darden TA, Lybrand TP. Staggered Mesh Ewald: An extension of the Smooth Particle-Mesh Ewald method adding great versatility. J Chem Theory Comput. 2009 Sep 9/8/2009; 5(9): 2322. PMID: 20174456, PMCID: PMC2822383, DOI: 10.1021/ct9001015, ISSN: 1549-9626.

Cerutti DS, Le Trong I, Stenkamp RE, Lybrand TP. Dynamics of the streptavidin-biotin complex in solution and in its crystal lattice: distinct behavior revealed by molecular simulations. J Phys Chem B. 2009 May 5/14/2009; 113(19): 6971-85. PMID: 19374419, PMCID: PMC2791092, DOI: 10.1021/jp9010372, ISSN: 1520-6106.

Cerutti DS, Le Trong I, Stenkamp RE, Lybrand TP. Simulations of a protein crystal: explicit treatment of crystallization conditions links theory and experiment in the streptavidin-biotin complex. Biochemistry [print-electronic]. 2008 Nov 11/18/2008; 47(46): 12065-77. PMID: 18950193, PMCID: PMC2765329, DOI: 10.1021/bi800894u, ISSN: 1520-4995.

Cerutti DS, Duke R, Freddolino PL, Fan H, Lybrand TP. Vulnerability in Popular Molecular Dynamics Packages Concerning Langevin and Andersen Dynamics. J Chem Theory Comput. 2008 Oct 10/14/2008; 4(10): 1669-80. PMID: 19180249, PMCID: PMC2632580, DOI: 10.1021/ct8002173, ISSN: 1549-9626.

Felts AS, Siegel BS, Young SM, Moth CW, Lybrand TP, Dannenberg AJ, Marnett LJ, Subbaramaiah K. Sulindac derivatives that activate the peroxisome proliferator-activated receptor gamma but lack cyclooxygenase inhibition. J. Med. Chem [print-electronic]. 2008 Aug 8/28/2008; 51(16): 4911-9. PMID: 18665581, PMCID: PMC2651753, DOI: 10.1021/jm700969c, ISSN: 1520-4804.

DeSensi SC, Rangel DP, Beth AH, Lybrand TP, Hustedt EJ. Simulation of nitroxide electron paramagnetic resonance spectra from brownian trajectories and molecular dynamics simulations. Biophys. J [print-electronic]. 2008 May 5/15/2008; 94(10): 3798-809. PMID: 18234808, PMCID: PMC2367180, PII: S0006-3495(08)70383-7, DOI: 10.1529/biophysj.107.125419, ISSN: 1542-0086.

Rigsby RE, Brown DW, Dawson E, Lybrand TP, Armstrong RN. A model for glutathione binding and activation in the fosfomycin resistance protein, FosA. Arch. Biochem. Biophys [print-electronic]. 2007 Aug 8/15/2007; 464(2): 277-83. PMID: 17537395, PMCID: PMC2709490, PII: S0003-9861(07)00235-4, DOI: 10.1016/j.abb.2007.04.035, ISSN: 0003-9861.

Harikumar KG, Dong M, Cheng Z, Pinon DI, Lybrand TP, Miller LJ. Transmembrane segment peptides can disrupt cholecystokinin receptor oligomerization without affecting receptor function. Biochemistry. 2006 Dec 12/12/2006; 45(49): 14706-16. PMID: 17144663, PMCID: PMC2585497, DOI: 10.1021/bi061107n, ISSN: 0006-2960.

Furse KE, Pratt DA, Schneider C, Brash AR, Porter NA, Lybrand TP. Molecular dynamics simulations of arachidonic acid-derived pentadienyl radical intermediate complexes with COX-1 and COX-2: insights into oxygenation regio- and stereoselectivity. Biochemistry. 2006 Mar 3/14/2006; 45(10): 3206-18. PMID: 16519515, PMCID: PMC2504531, DOI: 10.1021/bi052338h, ISSN: 0006-2960.

Furse KE, Pratt DA, Porter NA, Lybrand TP. Molecular dynamics simulations of arachidonic acid complexes with COX-1 and COX-2: insights into equilibrium behavior. Biochemistry. 2006 Mar 3/14/2006; 45(10): 3189-205. PMID: 16519514, PMCID: PMC2504530, DOI: 10.1021/bi052337p, ISSN: 0006-2960.

Hadac EM, Dawson ES, Darrow JW, Sugg EE, Lybrand TP, Miller LJ. Novel benzodiazepine photoaffinity probe stereoselectively labels a site deep within the membrane-spanning domain of the cholecystokinin receptor. J. Med. Chem. 2006 Feb 2/9/2006; 49(3): 850-63. PMID: 16451051, PMCID: PMC2528300, DOI: 10.1021/jm049072h, ISSN: 0022-2623.

Lai WC, Peach ML, Lybrand TP, Hazelbauer GL. Diagnostic cross-linking of paired cysteine pairs demonstrates homologous structures for two chemoreceptor domains with low sequence identity. Protein Sci [print-electronic]. 2006 Jan; 15(1): 94-101. PMID: 16322572, PMCID: PMC2242362, PII: ps.051802806, DOI: 10.1110/ps.051802806, ISSN: 0961-8368.

Hata AN, Lybrand TP, Breyer RM. Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2. J. Biol. Chem [print-electronic]. 2005 Sep 9/16/2005; 280(37): 32442-51. PMID: 16030019, PII: M502563200, DOI: 10.1074/jbc.M502563200, ISSN: 0021-9258.

Moth CW, Prusakiewicz JJ, Marnett LJ, Lybrand TP. Stereoselective binding of indomethacin ethanolamide derivatives to cyclooxygenase-1. J. Med. Chem. 2005 May 5/19/2005; 48(10): 3613-20. PMID: 15887968, DOI: 10.1021/jm0494164, ISSN: 0022-2623.

Hata AN, Lybrand TP, Marnett LJ, Breyer RM. Structural determinants of arylacetic acid nonsteroidal anti-inflammatory drugs necessary for binding and activation of the prostaglandin D2 receptor CRTH2. Mol. Pharmacol [print-electronic]. 2005 Mar; 67(3): 640-7. PMID: 15563582, PII: mol.104.007971, DOI: 10.1124/mol.104.007971, ISSN: 0026-895X.

Wingo TL, Shah VN, Anderson ME, Lybrand TP, Chazin WJ, Balser JR. An EF-hand in the sodium channel couples intracellular calcium to cardiac excitability. Nat. Struct. Mol. Biol [print-electronic]. 2004 Mar; 11(3): 219-25. PMID: 14981509, PII: nsmb737, DOI: 10.1038/nsmb737, ISSN: 1545-9993.

Harikumar KG, Pinon DI, Wessels WS, Dawson ES, Lybrand TP, Prendergast FG, Miller LJ. Measurement of intermolecular distances for the natural agonist Peptide docked at the cholecystokinin receptor expressed in situ using fluorescence resonance energy transfer. Mol. Pharmacol. 2004 Jan; 65(1): 28-35. PMID: 14722234, PII: 65/1/28, DOI: 10.1124/mol.65.1.28, ISSN: 0026-895X.

Dong M, Li Z, Zang M, Pinon DI, Lybrand TP, Miller LJ. Spatial approximation between two residues in the mid-region of secretin and the amino terminus of its receptor. Incorporation of seven sets of such constraints into a three-dimensional model of the agonist-bound secretin receptor. J. Biol. Chem [print-electronic]. 2003 Nov 11/28/2003; 278(48): 48300-12. PMID: 14500709, PII: M309166200, DOI: 10.1074/jbc.M309166200, ISSN: 0021-9258.

Furse KE, Lybrand TP. Three-dimensional models for beta-adrenergic receptor complexes with agonists and antagonists. J. Med. Chem. 2003 Oct 10/9/2003; 46(21): 4450-62. PMID: 14521408, DOI: 10.1021/jm0301437, ISSN: 0022-2623.

Dong M, Zang M, Pinon DI, Li Z, Lybrand TP, Miller LJ. Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus. Mol. Endocrinol. 2002 Nov; 16(11): 2490-501. PMID: 12403838, DOI: 10.1210/me.2002-0111, ISSN: 0888-8809.

Hyre DE, Amon LM, Penzotti JE, Le Trong I, Stenkamp RE, Lybrand TP, Stayton PS. Early mechanistic events in biotin dissociation from streptavidin. Nat. Struct. Biol. 2002 Aug; 9(8): 582-5. PMID: 12134141, PII: nsb825, DOI: 10.1038/nsb825, ISSN: 1072-8368.

Peach ML, Hazelbauer GL, Lybrand TP. Modeling the transmembrane domain of bacterial chemoreceptors. Protein Sci. 2002 Apr; 11(4): 912-23. PMID: 11910034, PMCID: PMC2373522, DOI: 10.1110/ps.4640102, ISSN: 0961-8368.

Ding XQ, Dolu V, Hadac EM, Holicky EL, Pinon DI, Lybrand TP, Miller LJ. Refinement of the structure of the ligand-occupied cholecystokinin receptor using a photolabile amino-terminal probe. J. Biol. Chem [print-electronic]. 2001 Feb 2/9/2001; 276(6): 4236-44. PMID: 11050076, PII: M003798200, DOI: 10.1074/jbc.M003798200, ISSN: 0021-9258.

McFarland BJ, Sant AJ, Lybrand TP, Beeson C. Ovalbumin(323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers. Biochemistry. 1999 Dec 12/14/1999; 38(50): 16663-70. PMID: 10600129, PII: bi991393l, ISSN: 0006-2960.

Freitag S, Chu V, Penzotti JE, Klumb LA, To R, Hyre D, Le Trong I, Lybrand TP, Stenkamp RE, Stayton PS. A structural snapshot of an intermediate on the streptavidin-biotin dissociation pathway. Proc. Natl. Acad. Sci. U.S.A. 1999 Jul 7/20/1999; 96(15): 8384-9. PMID: 10411884, PMCID: PMC17525, ISSN: 0027-8424.

Hadac EM, Ji Z, Pinon DI, Henne RM, Lybrand TP, Miller LJ. A peptide agonist acts by occupation of a monomeric G protein-coupled receptor: dual sites of covalent attachment to domains near TM1 and TM7 of the same molecule make biologically significant domain-swapped dimerization unlikely. J. Med. Chem. 1999 Jun 6/17/1999; 42(12): 2105-11. PMID: 10377216, PII: jm980732q, DOI: 10.1021/jm980732q, ISSN: 0022-2623.