Abstract
Protein–ligand interactions are of fundamental importance in a great many biological processes. However, despite enormous advances in the speed and accuracy of the three-dimensional structure determination of proteins and their complexes, our ability to predict binding affinity from structure remains severely limited. One reason for this dilemma is that affinities are governed not only by energetic considerations arising from the precise spatial disposition of interacting groups (loosely, enthalpy), but also by the dynamics of these groups (loosely, entropy) including solvent effects. In this work I will review current methodology for unravelling this complex problem, including X-ray crystallography, NMR, isothermal titration calorimetry and theoretical free energy perturbation methods.
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Frank HS, Evans MW (1945) J Chem Phys 13:507
Nemethy G, Scheraga HA (1962) J Chem Phys 36:3382
Tanford C (1980) The Hydrophobic Effect: Formation of Micelles and Biological Membranes. Wiley, New York
Privalov PL, Gill SJ (1988) Adv Protein Chem 39:191
Mirejovsky D, Arnett EM (1983) J Am Chem Soc 105:1112
Lee SH, Rossky PJ (1994) J Chem Phys 100:3334
Lee B (1991) Biopolymers 31:993
Lee B (1985) Biopolymers 24:813
Lucas M (1976) J Phys Chem 80:359
Southall NT, Dill KA, Haymet ADJ (2002) J Phys Chem B 106:521
Southall NT, Dill KA (2002) Biophys Chem 101:295
Chandler D (2005) Nature 437:640
Williams DH, Bardsley B (1999) Perspect Drug Discov Design 17:43
Wiseman T, Williston S, Brandts JF, Lin LN (1989) Anal Biochem 179:131
Penel S, Doig AJ (2001) J Mol Biol 305:961
Williams DH, Stephens E, Zhou M (2003) J Mol Biol 329:389
Hyre DE, Le Trong I, Freitag S, Stenkamp RE, Stayton PS (2000) Prot Sci 9:878
Vondrasek J, Bendova L, Klusak V, Hobza P (2005) J Am Chem Soc 127:2615
Ross PD, Subramanian S (1981) Biochemistry 20:3096
Chapman KT, Still WC (1989) J Am Chem Soc 111:3075
Hunter CA (2004) Angew Chem Int Ed 43:5310
Talhout R, Villa A, Mark AE, Engberts J (2003) J Am Chem Soc 125:10570
Daranas AH, Shimizu H, Homans SW (2004) J Am Chem Soc 126:11870
Burkhalter NF, Dimick SM, Toone EJ (2000) In: Ernst B, Hart GW, Sinay P (eds) Carbohydrates in Chemistry and Biology. Part I: Chemistry of Saccharides, Vol 2. Wiley, Weinheim, p 863
Cabani S, Gianni P, Mollica V, Lepori L (1981) J Sol Chem 10:563
Plyasunov AV, Shock EL (2000) Geochim Cosmochim Acta 64:439
Muller N (1990) Acc Chem Res 23:23
Buttery RG, Bomben JL, Guadagni DG, Ling LC (1971) J Agric Food Chem 19:1045
Orozco M, Luque FJ (2000) Chem Rev 100:4187
Kollman PA (1993) Chem Rev 93:2395
Carlson HA, Nguyen TB, Orozco M, Jorgensen WL (1993) J Comput Chem 14:1240
Orozco M, Jorgensen WL, Luque FJ (1993) J Comput Chem 14:1498
Jorgensen WL, Nguyen TB (1993) J Comput Chem 14:195
Wan S, Stote RH, Karplus M (2004) J Chem Phys 121:9539
Kubo MM, Gallicchio E, Levy RM (1997) J Phys Chem B 101:10527
Chothia C (1974) Nature 248:338
Levy RM, Zhang LY, Gallicchio E, Felts AK (2003) J Am Chem Soc 125:9523
Hawkins GD, Cramer CJ, Truhlar DG (1997) J Phys Chem B 101:7147
Chervenak MC, Toone EJ (1994) J Am Chem Soc 116:10533
Connelly P, Aldape RA, Bruzzese FJ, Chambers SP, Fitzgibbon MJ, Fleming MA, Itoh S, Livingston DJ, Navia MA, Thomson JA, Wilson KP (1994) Proc Natl Acad Sci 91:1964
Jencks WP (1981) Proc Natl Acad Sci 78:4046
Williams DH, Stephens E, O'Brien DP, Zhou M (2004) Angew Chem Int Ed 43:6596
Pitzer KS, Gwinn WD (1942) J Chem Phys 10:428
Searle MS, Williams DH (1992) J Am Chem Soc 114:10690
Akke M, Bruschweiler R, Palmer AG (1993) J Am Chem Soc 115:9832
Yang DW, Kay LE (1996) J Mol Biol 263:369
Spyracopoulos L, Gagne SM, Li MX, Sykes BD (1998) Biochemistry 37:18032
Bracken C, Carr PA, Cavanagh J, Palmer AG (1999) J Mol Biol 285:2133
Zídek L, Novotny MV, Stone MJ (1999) Nature Str Biol 6:1118
Sahu SC, Bhuyan AK, Udgaonkar JB, Hosur RV (2000) J Biomol NMR 18:107
Maler L, Blankenship J, Rance M, Chazin WJ (2000) Nature Str Biol 7:245
Lee AL, Kinnear SA, Wand AJ (2000) Nature Str Biol 7:72
Loh AP, Pawley N, Nicholson LK, Oswald RE (2001) Biochemistry 40:4590
Bingham R, Bodenhausen G, Findlay JHBC, Hsieh S-Y, Kalverda AP, Kjellberg A, Perazzolo C, Phillips SEV, Seshadri K, Turnbull WB, Homans SW (2004) J Am Chem Soc 126:1675
Palmer AG (1997) Curr Op Struct Biol 7:732
Cavanagh J, Akke M (2000) Nature Str Biol 7:11
Palmer AG (2001) Ann Rev Biophys 30:129
Palmer AG, Kroenke CD, Loria JP (2001) Meth Enzymol 339:204
Spyracopoulos L, Sykes BD (2001) Curr Op Struct Biol 11:555
Frueh D (2002) Progr NMR Spectrosc 41:305
Luginbuhl P, Wuthrich K (2002) Progr NMR Spectrosc 40:199
Case DA (2002) Acc Chem Res 35:325
Kempf JG, Loria JP (2003) Cell Biochem Biophys 37:187
Palmer AG (2004) Chem Rev 104:3623
Lipari G, Szabo A (1982) J Am Chem Soc 104:4546
Li ZG, Raychaudhuri S, Wand AJ (1996) Prot Sci 5:2647
Yang DW, Mok YK, FormanKay JD, Farrow NA, Kay LE (1997) J Mol Biol 272:790
Muhandiram DR, Yamazaki T, Sykes BD, Kay LE (1995) J Am Chem Soc 117:11536
Lee AL, Flynn PF, Wand AJ (1999) J Am Chem Soc 121:2891
Ishima R, Petkova AP, Louis JM, Torchia DA (2001) J Am Chem Soc 123:6164
Millet O, Muhandiram DR, Skrynnikov NR, Kay LE (2002) J Am Chem Soc 124:6439
Doig AJ, Sternberg MJE (1995) Prot Sci 4:2247
Wrabl JO, Shortle D, Woolf TB (2000) Proteins 38:123
Tidor B, Karplus M (1994) J Mol Biol 238:405
Millet O, Loria JP, Kroenke CD, Pons M, Palmer AG (2000) J Am Chem Soc 122:2867
Mulder FAA, van Tilborg PJA, Kaptein R, Boelens R (1999) J Biomol NMR 13:275
Akke M, Liu J, Cavanagh J, Erickson HP, Palmer AG (1998) Nature Str Biol 5:55
Davis DG, Perlman ME, London RE (1994) J Magn Reson B 104:266
Allerhand A, Gutowsky HS (1965) J Chem Phys 42:1587
Mulder FAA, Hon B, Muhandiram DR, Dahlquist FW, Kay LE (2000) Biochemistry 39:12614
Skrynnikov NR, Mulder FAA, Hon B, Dahlquist FW, Kay LE (2001) J Am Chem Soc 123:4556
Ishima R, Louis JM, Torchia DA (1999) J Am Chem Soc 121:11589
Ishima R, Torchia DA (1999) J Biomol NMR 14:369
Mulder FAA, Mittermaier A, Hon B, Dahlquist FW, Kay LE (2001) Nature Str Biol 8:932
Mulder FAA, Hon B, Mittermaier A, Dahlquist FW, Kay LE (2002) J Am Chem Soc 124:1443
Carr HY, Purcell EM (1954) Phys Rev 94:630
Yung A, Turnbull WB, Kalverda AP, Thompson GS, Homans SW, Kitov P, Bundle DR (2003) J Am Chem Soc 125:13058
Ling H, Boodhoo A, Hazes B, Cummings MD, Armstrong GD, Brunton JL, Read RJ (1998) Biochemistry 37:1777
Kitov PI, Shimizu H, Homans SW, Bundle DR (2003) J Am Chem Soc 125:3284
Stein PE, Boodhoo A, Tyrrell GJ, Brunton JL, Read RJ (1992) Nature 355:748
Richardson JM, Evans PD, Homans SW, DonohueRolfe A (1997) Nature Str Biol 4:190
Luz Z, Meiboom S (1963) J Chem Phys 39:366
Dzakula Z, Westler WM, Edison AS, Markley JL (1992) J Am Chem Soc 114:6195
Dzakula Z, Edison AS, Westler WM, Markley JL (1992) J Am Chem Soc 114:6200
Perez C, Lohr F, Ruterjans H, Schmidt JM (2001) J Am Chem Soc 123:7081
Chou JJ, Case DA, Bax A (2003) J Am Chem Soc 125:8959
Ben-Naim A, Marcus Y (1984) J Chem Phys 81:2016
Dunitz J (1994) Science 264:670
Holdgate GA, Tunnicliffe A, Ward WHJ, Weston SA, Rosenbrock G, Barth PT, Taylor IWF, Pauptit RA, Timms D (1997) Biochemistry 36:9663
Clarke C, Woods RJ, Gluska J, Cooper A, Nutley MA, Boons G-J (2001) J Am Chem Soc 123:12238
Otting G, Wuthrich K (1989) J Am Chem Soc 111:1871
Halle B, Andersson T, Forsen S, Lindman B (1981) J Am Chem Soc 103:500
Denisov VP, Halle B (1995) J Mol Biol 245:682
Denisov VP, Venu K, Peters J, Horlein HD, Halle B (1997) J Phys Chem B 101:9380
Li Z, Lazaridis T (2003) J Am Chem Soc 125:6636
Hamelberg D, McCammon JA (2004) J Am Chem Soc 126:7683
Barratt E, Bingham R, Warner DJ, Laughton CA, Phillips SEV, Homans SW (2005) J Am Chem Soc 127:11827
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Homans, S.W. (2006). Dynamics and Thermodynamics of Ligand–Protein Interactions. In: Peters, T. (eds) Bioactive Conformation I. Topics in Current Chemistry, vol 272. Springer, Berlin, Heidelberg . https://doi.org/10.1007/128_2006_090
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DOI: https://doi.org/10.1007/128_2006_090
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