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85. Charlop-Powers Z, Zeng L, Zhang Q, Zhou M-M (2010) Structural insights into selective
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87. Sun H, Liu J, Zhang J, Shen W, Huang H, Xu C, Dai H, Wu J, Shi Y (2007) Solution structure
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88. Ferguson FM, Dias DM, Rodrigues JPGLM, Wienk H, Boelens R, Bonvin AMJJ, Abell C,
Ciulli A (2014) Binding hotspots of BAZ2B bromodomain: histone interaction revealed by
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bi500909d
89. Marsh ENG, Suzuki Y (2014) Using 19F NMR to probe biological interactions of proteins and
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90. Gerig JT. (2001) Fluorine NMR. Online textbook; http://www.biophysics.org/img/jtg2001-2.
pdf
91. Moreira IS, Martins JM, Ramos RM, Fernandes PA, Ramos MJ (2013) Understanding
the importance of the aromatic amino-acid residues as hot-spots. Biochim Biophys Acta
1834(1):404–414. https://doi.org/10.1016/j.bbapap.2012.07.005
92. Bogan AA, Thorn KS (1998) Anatomy of hot spots in protein interfaces11Edited by J. Wells.
J Mol Biol 280(1):1–9. https://doi.org/10.1006/jmbi.1998.1843
93. Arntson KE, Pomerantz WCK (2016) Protein-observed fluorine NMR: a bioorthogonal
approach for small molecule discovery. J Med Chem 59(11):5158–5171. https://doi.org/10.
1021/acs.jmedchem.5b01447
94. Urick AK, Calle LP, Espinosa JF, Hu H, Pomerantz WCK (2016) Protein-observed fluorine
NMR is a complementary ligand discovery method to 1H CPMG ligand-observed NMR. ACS
Chem Biol 11(11):3154–3164. https://doi.org/10.1021/acschembio.6b00730
95. Zartler ER, Hanson J, Jones BE, Kline AD, Martin G, Mo H, Shapiro MJ, Wang R, Wu H,
Yan J (2003) RAMPED-UP NMR: multiplexed NMR-based screening for drug discovery.
J Am Chem Soc 125(36):10941–10946. https://doi.org/10.1021/ja0348593
96. Frey WD, Chaudhry A, Slepicka PF, Ouellette AM, Kirberger SE, Pomerantz WCK, Hannon
GJ, dos Santos CO (2017) BPTF maintains chromatin accessibility and the self-renewal
capacity of mammary gland stem cells. Stem Cell Rep 9(1):23–31. https://doi.org/10.1016/j.
stemcr.2017.04.031
97. Mayer M, Meyer B (2001) Group epitope mapping by saturation transfer difference NMR to
identify segments of a ligand in direct contact with a protein receptor. J Am Chem Soc
123(25):6108–6117. https://doi.org/10.1021/ja0100120
98. Geist L, Mayer M, Cockcroft X-L, Wolkerstorfer B, Kessler D, Engelhardt H, McConnell DB,
Konrat R (2017) Direct NMR probing of hydration shells of protein ligand interfaces and its
application to drug design. J Med Chem 60(21):8708–8715. https://doi.org/10.1021/acs.
jmedchem.7b00845
99. Spiliotopoulos D, Wamhoff E-C, Lolli G, Rademacher C, Caflisch A (2017) Discovery of
BAZ2A bromodomain ligands. Eur J Med Chem 139(Supplement C):564–572. https://doi.
org/10.1016/j.ejmech.2017.08.028
Applied Biophysics for Bromodomain Drug Discovery
333
N-X (2016) NMR-based platform for fragment-based lead discovery used in screening BRD4targeted compounds. Acta Pharmacol Sin 37(7):984–993. https://doi.org/10.1038/aps.2016.19
84. Poplawski A, Hu K, Lee W, Natesan S, Peng D, Carlson S, Shi X, Balaz S, Markley JL,
Glass KC (2014) Molecular insights into the recognition of N-terminal histone modifications
by the BRPF1 bromodomain. J Mol Biol 426(8):1661–1676. https://doi.org/10.1016/j.jmb.
2013.12.007
85. Charlop-Powers Z, Zeng L, Zhang Q, Zhou M-M (2010) Structural insights into selective
histone H3 recognition by the human polybromo bromodomain 2. Cell Res 20:529. https://doi.
org/10.1038/cr.2010.43
86. Liu Y, Wang X, Zhang J, Huang H, Ding B, Wu J, Shi Y (2008) Structural basis and binding
properties of the second bromodomain of Brd4 with acetylated histone tails. Biochemistry
47(24):6403–6417. https://doi.org/10.1021/bi8001659
87. Sun H, Liu J, Zhang J, Shen W, Huang H, Xu C, Dai H, Wu J, Shi Y (2007) Solution structure
of BRD7 bromodomain and its interaction with acetylated peptides from histone H3 and H4.
Biochem Biophys Res Commun 358(2):435–441. https://doi.org/10.1016/j.bbrc.2007.04.139
88. Ferguson FM, Dias DM, Rodrigues JPGLM, Wienk H, Boelens R, Bonvin AMJJ, Abell C,
Ciulli A (2014) Binding hotspots of BAZ2B bromodomain: histone interaction revealed by
solution NMR driven docking. Biochemistry 53(42):6706–6716. https://doi.org/10.1021/
bi500909d
89. Marsh ENG, Suzuki Y (2014) Using 19F NMR to probe biological interactions of proteins and
peptides. ACS Chem Biol 9(6):1242–1250. https://doi.org/10.1021/cb500111u
90. Gerig JT. (2001) Fluorine NMR. Online textbook; http://www.biophysics.org/img/jtg2001-2.
91. Moreira IS, Martins JM, Ramos RM, Fernandes PA, Ramos MJ (2013) Understanding
the importance of the aromatic amino-acid residues as hot-spots. Biochim Biophys Acta
1834(1):404–414. https://doi.org/10.1016/j.bbapap.2012.07.005
92. Bogan AA, Thorn KS (1998) Anatomy of hot spots in protein interfaces11Edited by J. Wells.
J Mol Biol 280(1):1–9. https://doi.org/10.1006/jmbi.1998.1843
93. Arntson KE, Pomerantz WCK (2016) Protein-observed fluorine NMR: a bioorthogonal
approach for small molecule discovery. J Med Chem 59(11):5158–5171. https://doi.org/10.
1021/acs.jmedchem.5b01447
94. Urick AK, Calle LP, Espinosa JF, Hu H, Pomerantz WCK (2016) Protein-observed fluorine
NMR is a complementary ligand discovery method to 1H CPMG ligand-observed NMR. ACS
Chem Biol 11(11):3154–3164. https://doi.org/10.1021/acschembio.6b00730
95. Zartler ER, Hanson J, Jones BE, Kline AD, Martin G, Mo H, Shapiro MJ, Wang R, Wu H,
Yan J (2003) RAMPED-UP NMR: multiplexed NMR-based screening for drug discovery.
J Am Chem Soc 125(36):10941–10946. https://doi.org/10.1021/ja0348593
96. Frey WD, Chaudhry A, Slepicka PF, Ouellette AM, Kirberger SE, Pomerantz WCK, Hannon
GJ, dos Santos CO (2017) BPTF maintains chromatin accessibility and the self-renewal
capacity of mammary gland stem cells. Stem Cell Rep 9(1):23–31. https://doi.org/10.1016/j.
stemcr.2017.04.031
97. Mayer M, Meyer B (2001) Group epitope mapping by saturation transfer difference NMR to
identify segments of a ligand in direct contact with a protein receptor. J Am Chem Soc
123(25):6108–6117. https://doi.org/10.1021/ja0100120
98. Geist L, Mayer M, Cockcroft X-L, Wolkerstorfer B, Kessler D, Engelhardt H, McConnell DB,
Konrat R (2017) Direct NMR probing of hydration shells of protein ligand interfaces and its
application to drug design. J Med Chem 60(21):8708–8715. https://doi.org/10.1021/acs.
jmedchem.7b00845
99. Spiliotopoulos D, Wamhoff E-C, Lolli G, Rademacher C, Caflisch A (2017) Discovery of
BAZ2A bromodomain ligands. Eur J Med Chem 139(Supplement C):564–572. https://doi.
org/10.1016/j.ejmech.2017.08.028
Applied Biophysics for Bromodomain Drug Discovery
333