Displacement of disordered water molecules from hydrophobic pocket creates enthalpic signature: Binding of phosphonamidate to the S1'-pocket of thermolysin
Prerequisite for the design of tight binding protein inhibitors and prediction of their properties is an in-depth understanding of the structural and thermodynamic details of the binding process. A series of closely related phosphonamidates was studied to elucidate the forces underlying their bindin...
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| Veröffentlicht in: | Biochimica et biophysica acta Jg. 1800; H. 11; S. 1192 - 1202 |
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01.11.2010
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| Abstract | Prerequisite for the design of tight binding protein inhibitors and prediction of their properties is an in-depth understanding of the structural and thermodynamic details of the binding process. A series of closely related phosphonamidates was studied to elucidate the forces underlying their binding affinity to thermolysin. The investigated inhibitors are identical except for the parts penetrating into the hydrophobic S₁'-pocket.
A correlation of structural, kinetic and thermodynamic data was carried out by X-ray crystallography, kinetic inhibition assay and isothermal titration calorimetry.
Binding affinity increases with larger ligand hydrophobic P₁'-moieties accommodating the S₁'-pocket. Surprisingly, larger P₁'-side chain modifications are accompanied by an increase in the enthalpic contribution to binding. In agreement with other studies, it is suggested that the release of largely disordered waters from an imperfectly hydrated pocket results in an enthalpically favourable integration of these water molecules into bulk water upon inhibitor binding. This enthalpically favourable process contributes more strongly to the binding energetics than the entropy increase resulting from the release of water molecules from the S₁'-pocket or the formation of apolar interactions between protein and inhibitor.
Displacement of highly disordered water molecules from a rather imperfectly hydrated and hydrophobic specificity pocket can reveal an enthalpic signature of inhibitor binding. |
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| AbstractList | Prerequisite for the design of tight binding protein inhibitors and prediction of their properties is an in-depth understanding of the structural and thermodynamic details of the binding process. A series of closely related phosphonamidates was studied to elucidate the forces underlying their binding affinity to thermolysin. The investigated inhibitors are identical except for the parts penetrating into the hydrophobic S₁'-pocket.BACKGROUNDPrerequisite for the design of tight binding protein inhibitors and prediction of their properties is an in-depth understanding of the structural and thermodynamic details of the binding process. A series of closely related phosphonamidates was studied to elucidate the forces underlying their binding affinity to thermolysin. The investigated inhibitors are identical except for the parts penetrating into the hydrophobic S₁'-pocket.A correlation of structural, kinetic and thermodynamic data was carried out by X-ray crystallography, kinetic inhibition assay and isothermal titration calorimetry.METHODSA correlation of structural, kinetic and thermodynamic data was carried out by X-ray crystallography, kinetic inhibition assay and isothermal titration calorimetry.Binding affinity increases with larger ligand hydrophobic P₁'-moieties accommodating the S₁'-pocket. Surprisingly, larger P₁'-side chain modifications are accompanied by an increase in the enthalpic contribution to binding. In agreement with other studies, it is suggested that the release of largely disordered waters from an imperfectly hydrated pocket results in an enthalpically favourable integration of these water molecules into bulk water upon inhibitor binding. This enthalpically favourable process contributes more strongly to the binding energetics than the entropy increase resulting from the release of water molecules from the S₁'-pocket or the formation of apolar interactions between protein and inhibitor.RESULTS AND CONCLUSIONSBinding affinity increases with larger ligand hydrophobic P₁'-moieties accommodating the S₁'-pocket. Surprisingly, larger P₁'-side chain modifications are accompanied by an increase in the enthalpic contribution to binding. In agreement with other studies, it is suggested that the release of largely disordered waters from an imperfectly hydrated pocket results in an enthalpically favourable integration of these water molecules into bulk water upon inhibitor binding. This enthalpically favourable process contributes more strongly to the binding energetics than the entropy increase resulting from the release of water molecules from the S₁'-pocket or the formation of apolar interactions between protein and inhibitor.Displacement of highly disordered water molecules from a rather imperfectly hydrated and hydrophobic specificity pocket can reveal an enthalpic signature of inhibitor binding.GENERAL SIGNIFICANCEDisplacement of highly disordered water molecules from a rather imperfectly hydrated and hydrophobic specificity pocket can reveal an enthalpic signature of inhibitor binding. Prerequisite for the design of tight binding protein inhibitors and prediction of their properties is an in-depth understanding of the structural and thermodynamic details of the binding process. A series of closely related phosphonamidates was studied to elucidate the forces underlying their binding affinity to thermolysin. The investigated inhibitors are identical except for the parts penetrating into the hydrophobic S₁'-pocket. A correlation of structural, kinetic and thermodynamic data was carried out by X-ray crystallography, kinetic inhibition assay and isothermal titration calorimetry. Binding affinity increases with larger ligand hydrophobic P₁'-moieties accommodating the S₁'-pocket. Surprisingly, larger P₁'-side chain modifications are accompanied by an increase in the enthalpic contribution to binding. In agreement with other studies, it is suggested that the release of largely disordered waters from an imperfectly hydrated pocket results in an enthalpically favourable integration of these water molecules into bulk water upon inhibitor binding. This enthalpically favourable process contributes more strongly to the binding energetics than the entropy increase resulting from the release of water molecules from the S₁'-pocket or the formation of apolar interactions between protein and inhibitor. Displacement of highly disordered water molecules from a rather imperfectly hydrated and hydrophobic specificity pocket can reveal an enthalpic signature of inhibitor binding. |
| Author | Englert, L. Biela, A. Heine, A. Zayed, M. Hangauer, D. Klebe, G. |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20600625$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1021/bi051346v 10.1107/S0021889892009944 10.1038/newbio238041a0 10.1111/j.1432-1033.1986.tb09664.x 10.1093/protein/11.12.1235 10.1101/SQB.1987.052.01.012 10.1126/science.653353 10.1038/nrd3054 10.1107/S0907444998003254 10.1016/0022-2836(77)90286-8 10.1107/S0907444904019158 10.1107/S090744490200584X 10.1126/science.3810156 10.1016/0003-9861(71)90331-6 10.1007/s00894-008-0279-y 10.1016/0141-8130(82)90048-4 10.1021/ja0527525 10.1021/bi00289a002 10.1016/0022-2836(87)90124-0 10.1002/anie.200602227 10.1016/j.ab.2006.02.029 10.1126/science.8052849 10.1006/immu.1993.1053 10.1126/science.271.5245.72 10.1021/ja060070r 10.1002/cmdc.201000084 10.1002/anie.200701169 10.1002/(SICI)1097-0134(199604)24:4<433::AID-PROT3>3.0.CO;2-F 10.1016/S0006-291X(67)80122-0 10.1021/bi00159a016 10.1073/pnas.0407968101 10.1016/j.jmb.2009.04.051 10.1073/pnas.0610202104 10.1016/0003-2697(89)90213-3 10.1021/ma60030a031 10.1021/bi00400a008 10.1016/0022-2836(82)90319-9 10.1002/pro.61 10.1002/anie.200300644 10.1073/pnas.0806307105 10.1016/0003-9861(75)90085-5 10.1021/cr9804543 10.1016/j.drudis.2007.05.004 10.1021/ci980154m 10.1016/j.jmb.2009.06.016 10.1002/bip.360310802 |
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| References | Williams (10.1016/j.bbagen.2010.06.009_bib38) 2004; 43 Wolfenden (10.1016/j.bbagen.2010.06.009_bib30) 1994; 265 Patchett (10.1016/j.bbagen.2010.06.009_bib9) 1985; 57 Matthews (10.1016/j.bbagen.2010.06.009_bib28) 2009; 18 Gerlach (10.1016/j.bbagen.2010.06.009_bib5) 2007; 46 Young (10.1016/j.bbagen.2010.06.009_bib37) 2007; 104 Emsley (10.1016/j.bbagen.2010.06.009_bib43) 2004; 60 Laskowski (10.1016/j.bbagen.2010.06.009_bib49) 1993; 26 Jeffrey (10.1016/j.bbagen.2010.06.009_bib20) 1982; 4 Morihara (10.1016/j.bbagen.2010.06.009_bib7) 1967; 26 Juers (10.1016/j.bbagen.2010.06.009_bib10) 2005; 44 Holden (10.1016/j.bbagen.2010.06.009_bib15) 1987; 26 Whittaker (10.1016/j.bbagen.2010.06.009_bib12) 1999; 99 Zhang (10.1016/j.bbagen.2010.06.009_bib31) 1996; 24 Vaitheeswaran (10.1016/j.bbagen.2010.06.009_bib32) 2004; 101 Burling (10.1016/j.bbagen.2010.06.009_bib34) 1996; 271 Holmes (10.1016/j.bbagen.2010.06.009_bib39) 1982; 160 Shimokhina (10.1016/j.bbagen.2010.06.009_bib26) 2006; 45 Sheriff (10.1016/j.bbagen.2010.06.009_bib45) 1993; 3 Ladbury (10.1016/j.bbagen.2010.06.009_bib4) 2010; 9 Komiyama (10.1016/j.bbagen.2010.06.009_bib23) 1975; 171 Harrison (10.1016/j.bbagen.2010.06.009_bib11) 1992; 31 Tronrud (10.1016/j.bbagen.2010.06.009_bib14) 1986; 157 Sheriff (10.1016/j.bbagen.2010.06.009_bib46) 1987; 197 Baum (10.1016/j.bbagen.2010.06.009_bib3) 2009; 391 Englert (10.1016/j.bbagen.2010.06.009_bib24) 2010; 5 Tronrud (10.1016/j.bbagen.2010.06.009_bib18) 1987; 235 Matthews (10.1016/j.bbagen.2010.06.009_bib6) 1972; 238 Sheldrick (10.1016/j.bbagen.2010.06.009_bib42) 1997; Vol. 277 Weimer (10.1016/j.bbagen.2010.06.009_bib47) 2006; 352 Tanford (10.1016/j.bbagen.2010.06.009_bib27) 1978; 200 Homans (10.1016/j.bbagen.2010.06.009_bib36) 2007; 12 Otwinowski (10.1016/j.bbagen.2010.06.009_bib40) 1997; Vol. 276 Weaver (10.1016/j.bbagen.2010.06.009_bib19) 1977; 114 Hausrath (10.1016/j.bbagen.2010.06.009_bib22) 2002; 58 Sansom (10.1016/j.bbagen.2010.06.009_bib13) 1998; 11 Wade (10.1016/j.bbagen.2010.06.009_bib29) 1991; 31 Brunger (10.1016/j.bbagen.2010.06.009_bib41) 1998; 54 Clark (10.1016/j.bbagen.2010.06.009_bib21) 2008; 14 Bartlett (10.1016/j.bbagen.2010.06.009_bib16) 1987; 52 Bartlett (10.1016/j.bbagen.2010.06.009_bib17) 1983; 22 Matthews (10.1016/j.bbagen.2010.06.009_bib44) 1972; 5 Liu (10.1016/j.bbagen.2010.06.009_bib33) 2008; 105 Drucker (10.1016/j.bbagen.2010.06.009_bib8) 1971; 147 Barratt (10.1016/j.bbagen.2010.06.009_bib35) 2005; 127 Leatherbarrow (10.1016/j.bbagen.2010.06.009_bib48) 1998 Wiseman (10.1016/j.bbagen.2010.06.009_bib50) 1989; 179 Krishnamurthy (10.1016/j.bbagen.2010.06.009_bib1) 2006; 128 Viswanadhan (10.1016/j.bbagen.2010.06.009_bib25) 1999; 39 Baum (10.1016/j.bbagen.2010.06.009_bib2) 2009; 390 |
| References_xml | – volume: 44 start-page: 16524 year: 2005 ident: 10.1016/j.bbagen.2010.06.009_bib10 article-title: Structural analysis of silanediols as transition-state-analogue inhibitors of the benchmark metalloprotease thermolysin publication-title: Biochemistry doi: 10.1021/bi051346v – volume: 26 start-page: 283 year: 1993 ident: 10.1016/j.bbagen.2010.06.009_bib49 article-title: PROCHECK: a program to check the stereochemical quality of protein structures publication-title: J. Appl. Crystallogr doi: 10.1107/S0021889892009944 – volume: 238 start-page: 41 year: 1972 ident: 10.1016/j.bbagen.2010.06.009_bib6 article-title: Structure of thermolysin publication-title: Nat. New Biol. doi: 10.1038/newbio238041a0 – volume: 157 start-page: 261 year: 1986 ident: 10.1016/j.bbagen.2010.06.009_bib14 article-title: Crystallographic structural analysis of phosphoramidates as inhibitors and transition-state analogs of thermolysin publication-title: Eur. J. Biochem. doi: 10.1111/j.1432-1033.1986.tb09664.x – volume: 11 start-page: 1235 year: 1998 ident: 10.1016/j.bbagen.2010.06.009_bib13 article-title: Molecular modelling and site-directed mutagenesis of the active site of endothelin-converting enzyme publication-title: Protein Eng. doi: 10.1093/protein/11.12.1235 – volume: 52 start-page: 83 year: 1987 ident: 10.1016/j.bbagen.2010.06.009_bib16 article-title: Phosphorus-containing peptide analogs as peptidase inhibitors publication-title: Cold Spring Harbor Symp. Quant. Biol. doi: 10.1101/SQB.1987.052.01.012 – volume: Vol. 276 start-page: 307 year: 1997 ident: 10.1016/j.bbagen.2010.06.009_bib40 – volume: 200 start-page: 1012 year: 1978 ident: 10.1016/j.bbagen.2010.06.009_bib27 article-title: The hydrophobic effect and the organization of living matter publication-title: Science doi: 10.1126/science.653353 – volume: Vol. 277 start-page: 319 year: 1997 ident: 10.1016/j.bbagen.2010.06.009_bib42 – volume: 9 start-page: 23 year: 2010 ident: 10.1016/j.bbagen.2010.06.009_bib4 article-title: Adding calorimetric data to decision making in lead discovery: a hot tip publication-title: Nat. Rev. Drug Discov. doi: 10.1038/nrd3054 – volume: 54 start-page: 905 year: 1998 ident: 10.1016/j.bbagen.2010.06.009_bib41 article-title: Crystallography & NMR system: a new software suite for macromolecular structure determination publication-title: Acta Crystallogr., Sect. D: Biol. Crystallogr. doi: 10.1107/S0907444998003254 – volume: 114 start-page: 119 year: 1977 ident: 10.1016/j.bbagen.2010.06.009_bib19 article-title: A crystallographic study of the complex of phosphoramidon with thermolysin. A model for the presumed catalytic transition state and for the binding of extended substances publication-title: J. Mol. Biol. doi: 10.1016/0022-2836(77)90286-8 – volume: 60 start-page: 2126 year: 2004 ident: 10.1016/j.bbagen.2010.06.009_bib43 article-title: Coot: model-building tools for molecular graphics publication-title: Acta Crystallogr., Sect. D: Biol. Crystallogr. doi: 10.1107/S0907444904019158 – year: 1998 ident: 10.1016/j.bbagen.2010.06.009_bib48 – volume: 58 start-page: 1002 year: 2002 ident: 10.1016/j.bbagen.2010.06.009_bib22 article-title: Thermolysin in the absence of substrate has an open conformation publication-title: Acta Crystallogr., Sect. D: Biol. Crystallogr. doi: 10.1107/S090744490200584X – volume: 235 start-page: 571 year: 1987 ident: 10.1016/j.bbagen.2010.06.009_bib18 article-title: Structures of two thermolysin–inhibitor complexes that differ by a single hydrogen bond publication-title: Science doi: 10.1126/science.3810156 – volume: 147 start-page: 242 year: 1971 ident: 10.1016/j.bbagen.2010.06.009_bib8 article-title: The role of calcium in thermolysin: effect on kinetic properties and autodigestion publication-title: Arch. Biochem. Biophys. doi: 10.1016/0003-9861(71)90331-6 – volume: 14 start-page: 689 year: 2008 ident: 10.1016/j.bbagen.2010.06.009_bib21 article-title: Why are dimethyl sulfoxide and dimethyl sulfone such good solvents? publication-title: J. Mol. Model. doi: 10.1007/s00894-008-0279-y – volume: 4 start-page: 173 year: 1982 ident: 10.1016/j.bbagen.2010.06.009_bib20 publication-title: Int. J. Biol. Macromol. doi: 10.1016/0141-8130(82)90048-4 – volume: 127 start-page: 11827 year: 2005 ident: 10.1016/j.bbagen.2010.06.009_bib35 article-title: Van der Waals interactions dominate ligand–protein association in a protein binding site occluded from solvent water publication-title: J. Am. Chem. Soc. doi: 10.1021/ja0527525 – volume: 22 start-page: 4618 year: 1983 ident: 10.1016/j.bbagen.2010.06.009_bib17 article-title: Phosphonamidates as transition-state analogue inhibitors of thermolysin publication-title: Biochemistry doi: 10.1021/bi00289a002 – volume: 197 start-page: 273 year: 1987 ident: 10.1016/j.bbagen.2010.06.009_bib46 article-title: Structure of myohemerythrin in the azidomet state at 1.7/1.3 A resolution publication-title: J. Mol. Biol. doi: 10.1016/0022-2836(87)90124-0 – volume: 45 start-page: 6374 year: 2006 ident: 10.1016/j.bbagen.2010.06.009_bib26 article-title: Contribution of ligand desolvation to binding thermodynamics in a ligand–protein interaction publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.200602227 – volume: 352 start-page: 110 year: 2006 ident: 10.1016/j.bbagen.2010.06.009_bib47 article-title: A quenched fluorescent dipeptide for assaying dispase- and thermolysin-like proteases publication-title: Anal. Biochem. doi: 10.1016/j.ab.2006.02.029 – volume: 265 start-page: 936 year: 1994 ident: 10.1016/j.bbagen.2010.06.009_bib30 article-title: On the probability of finding a water molecule in a nonpolar cavity publication-title: Science doi: 10.1126/science.8052849 – volume: 3 start-page: 191 year: 1993 ident: 10.1016/j.bbagen.2010.06.009_bib45 article-title: Some methods for examining the interactions between two molecules publication-title: Immunomethods doi: 10.1006/immu.1993.1053 – volume: 271 start-page: 72 year: 1996 ident: 10.1016/j.bbagen.2010.06.009_bib34 article-title: Direct observation of protein solvation and discrete disorder with experimental crystallographic phases publication-title: Science doi: 10.1126/science.271.5245.72 – volume: 128 start-page: 5802 year: 2006 ident: 10.1016/j.bbagen.2010.06.009_bib1 article-title: The paradoxical thermodynamic basis for the interaction of ethylene glycol, glycine, and sarcosine chains with bovine carbonic anhydrase II: an unexpected manifestation of enthalpy/entropy compensation publication-title: J. Am. Chem. Soc. doi: 10.1021/ja060070r – volume: 5 start-page: 930 year: 2010 ident: 10.1016/j.bbagen.2010.06.009_bib24 article-title: Fragment-based lead discovery: screening and optimizing fragments for thermolysin inhibition publication-title: ChemMedChem doi: 10.1002/cmdc.201000084 – volume: 46 start-page: 8511 year: 2007 ident: 10.1016/j.bbagen.2010.06.009_bib5 article-title: Thermodynamic inhibition profile of a cyclopentyl and a cyclohexyl derivative towards thrombin: the same but for different reasons publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.200701169 – volume: 24 start-page: 433 year: 1996 ident: 10.1016/j.bbagen.2010.06.009_bib31 article-title: Hydrophilicity of cavities in proteins publication-title: Proteins doi: 10.1002/(SICI)1097-0134(199604)24:4<433::AID-PROT3>3.0.CO;2-F – volume: 26 start-page: 656 year: 1967 ident: 10.1016/j.bbagen.2010.06.009_bib7 article-title: The specificities of various neutral and alkaline proteinases from microorganisms publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/S0006-291X(67)80122-0 – volume: 31 start-page: 10757 year: 1992 ident: 10.1016/j.bbagen.2010.06.009_bib11 article-title: Mechanistic studies on the human matrix metalloproteinase stromelysin publication-title: Biochemistry doi: 10.1021/bi00159a016 – volume: 57 start-page: 1 year: 1985 ident: 10.1016/j.bbagen.2010.06.009_bib9 article-title: The design and properties of N-carboxyalkyldipeptide inhibitors of angiotensin-converting enzyme publication-title: Adv. Enzymol. Relat. Areas Mol. Biol. – volume: 101 start-page: 17002 year: 2004 ident: 10.1016/j.bbagen.2010.06.009_bib32 article-title: Water clusters in nonpolar cavities publication-title: Proc. Natl Acad. Sci. U. S. A. doi: 10.1073/pnas.0407968101 – volume: 390 start-page: 56 year: 2009 ident: 10.1016/j.bbagen.2010.06.009_bib2 article-title: More than a simple lipophilic contact: a detailed thermodynamic analysis of nonbasic residues in the S1 pocket of thrombin publication-title: J. Mol. Biol. doi: 10.1016/j.jmb.2009.04.051 – volume: 104 start-page: 808 year: 2007 ident: 10.1016/j.bbagen.2010.06.009_bib37 article-title: Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand binding publication-title: Proc. Natl Acad. Sci. U. S. A. doi: 10.1073/pnas.0610202104 – volume: 179 start-page: 131 year: 1989 ident: 10.1016/j.bbagen.2010.06.009_bib50 article-title: Rapid measurement of binding constants and heats of binding using a new titration calorimeter publication-title: Anal. Biochem. doi: 10.1016/0003-2697(89)90213-3 – volume: 5 start-page: 818 year: 1972 ident: 10.1016/j.bbagen.2010.06.009_bib44 article-title: The gamma-turn. Evidence for a new folded conformation in proteins publication-title: Macromolecules doi: 10.1021/ma60030a031 – volume: 26 start-page: 8542 year: 1987 ident: 10.1016/j.bbagen.2010.06.009_bib15 article-title: Slow- and fast-binding inhibitors of thermolysin display different modes of binding: crystallographic analysis of extended phosphonamidate transition-state analogues publication-title: Biochemistry doi: 10.1021/bi00400a008 – volume: 160 start-page: 623 year: 1982 ident: 10.1016/j.bbagen.2010.06.009_bib39 article-title: Structure of thermolysin refined at 1.6 A resolution publication-title: J. Mol. Biol. doi: 10.1016/0022-2836(82)90319-9 – volume: 18 start-page: 494 year: 2009 ident: 10.1016/j.bbagen.2010.06.009_bib28 article-title: A review about nothing: are apolar cavities in proteins really empty? publication-title: Protein Sci. doi: 10.1002/pro.61 – volume: 43 start-page: 6596 year: 2004 ident: 10.1016/j.bbagen.2010.06.009_bib38 article-title: Understanding noncovalent interactions: ligand binding energy and catalytic efficiency from ligand-induced reductions in motion within receptors and enzymes publication-title: Angew. Chem. Int. Ed. Engl. doi: 10.1002/anie.200300644 – volume: 105 start-page: 14406 year: 2008 ident: 10.1016/j.bbagen.2010.06.009_bib33 article-title: Use of experimental crystallographic phases to examine the hydration of polar and nonpolar cavities in T4 lysozyme publication-title: Proc. Natl Acad. Sci. U. S. A. doi: 10.1073/pnas.0806307105 – volume: 171 start-page: 727 year: 1975 ident: 10.1016/j.bbagen.2010.06.009_bib23 article-title: Studies on inhibitory effect of phosphoramidon and its analogs on thermolysin publication-title: Arch. Biochem. Biophys. doi: 10.1016/0003-9861(75)90085-5 – volume: 99 start-page: 2735 year: 1999 ident: 10.1016/j.bbagen.2010.06.009_bib12 article-title: Design and therapeutic application of matrix metalloproteinase inhibitors publication-title: Chem. Rev. doi: 10.1021/cr9804543 – volume: 12 start-page: 534 year: 2007 ident: 10.1016/j.bbagen.2010.06.009_bib36 article-title: Water, water everywhere—except where it matters? publication-title: Drug Discovery Today doi: 10.1016/j.drudis.2007.05.004 – volume: 39 start-page: 405 year: 1999 ident: 10.1016/j.bbagen.2010.06.009_bib25 article-title: Prediction of solvation free energies of small organic molecules: additive-constitutive models based on molecular fingerprints and atomic constants publication-title: J. Chem. Inf. Comput. Sci. doi: 10.1021/ci980154m – volume: 391 start-page: 552 year: 2009 ident: 10.1016/j.bbagen.2010.06.009_bib3 article-title: Think twice: understanding the high potency of bis(phenyl)methane inhibitors of thrombin publication-title: J. Mol. Biol. doi: 10.1016/j.jmb.2009.06.016 – volume: 31 start-page: 919 year: 1991 ident: 10.1016/j.bbagen.2010.06.009_bib29 article-title: A molecular dynamics study of thermodynamic and structural aspects of the hydration of cavities in proteins publication-title: Biopolymers doi: 10.1002/bip.360310802 |
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| SubjectTerms | Binding Sites Crystallography, X-Ray Entropy Hydrophobic and Hydrophilic Interactions Models, Molecular Organophosphorus Compounds - chemistry Organophosphorus Compounds - metabolism Phosphoamino Acids - chemistry Protein Binding Protein Structure, Tertiary Thermodynamics Thermolysin - metabolism Water - chemistry Water - metabolism |
| Title | Displacement of disordered water molecules from hydrophobic pocket creates enthalpic signature: Binding of phosphonamidate to the S1'-pocket of thermolysin |
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