2bza: Difference between revisions
New page: left|200px<br /><applet load="2bza" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bza, resolution 1.90Å" /> '''BOVINE PANCREAS BETA... |
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[[Image:2bza.gif|left|200px]]<br /><applet load="2bza" size=" | [[Image:2bza.gif|left|200px]]<br /><applet load="2bza" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="2bza, resolution 1.90Å" /> | caption="2bza, resolution 1.90Å" /> | ||
'''BOVINE PANCREAS BETA-TRYPSIN IN COMPLEX WITH BENZYLAMINE'''<br /> | '''BOVINE PANCREAS BETA-TRYPSIN IN COMPLEX WITH BENZYLAMINE'''<br /> | ||
==Overview== | ==Overview== | ||
The relative free energies of binding of trypsin to two amine inhibitors, benzamidine (BZD) and benzylamine (BZA), were calculated using | The relative free energies of binding of trypsin to two amine inhibitors, benzamidine (BZD) and benzylamine (BZA), were calculated using non-Boltzmann thermodynamic integration (NBTI). Comparison of the simulations with the crystal structures of both complexes, trypsin-BZD and trypsin-BZA, shows that NBTI simulations better sample conformational space relative to thermodynamic integration (TI) simulations. The relative binding free energy calculated using NBTI was much closer to the experimentally determined value than that obtained using TI. The error in the TI simulation was found to be primarily due to incorrect sampling of BZA's conformation in the binding pocket. In contrast, NBTI produces a smooth mutation from BZD to BZA using a surrogate potential, resulting in a much closer agreement between the inhibitors' conformations and the omit electron density maps. This superior agreement between experiment and simulation, of both relative binding free energy differences and conformational sampling, demonstrates NBTI's usefulness for free energy calculations in macromolecular simulations. | ||
==About this Structure== | ==About this Structure== | ||
2BZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with CA, CL, SO4 and ABN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http:// | 2BZA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=ABN:'>ABN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Trypsin Trypsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.4 3.4.21.4] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2BZA OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Trypsin]] | [[Category: Trypsin]] | ||
[[Category: Brunger, A | [[Category: Brunger, A T.]] | ||
[[Category: Ferreira-Da-Silva, J | [[Category: Ferreira-Da-Silva, J M.S.]] | ||
[[Category: Mares-Guia, M.]] | [[Category: Mares-Guia, M.]] | ||
[[Category: Ota, N.]] | [[Category: Ota, N.]] | ||
[[Category: Shah, S | [[Category: Shah, S S.]] | ||
[[Category: Stroupe, C.]] | [[Category: Stroupe, C.]] | ||
[[Category: ABN]] | [[Category: ABN]] | ||
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[[Category: hydrolase (serine proteinase)]] | [[Category: hydrolase (serine proteinase)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:43:14 2008'' | ||
Revision as of 17:43, 21 February 2008
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BOVINE PANCREAS BETA-TRYPSIN IN COMPLEX WITH BENZYLAMINE
OverviewOverview
The relative free energies of binding of trypsin to two amine inhibitors, benzamidine (BZD) and benzylamine (BZA), were calculated using non-Boltzmann thermodynamic integration (NBTI). Comparison of the simulations with the crystal structures of both complexes, trypsin-BZD and trypsin-BZA, shows that NBTI simulations better sample conformational space relative to thermodynamic integration (TI) simulations. The relative binding free energy calculated using NBTI was much closer to the experimentally determined value than that obtained using TI. The error in the TI simulation was found to be primarily due to incorrect sampling of BZA's conformation in the binding pocket. In contrast, NBTI produces a smooth mutation from BZD to BZA using a surrogate potential, resulting in a much closer agreement between the inhibitors' conformations and the omit electron density maps. This superior agreement between experiment and simulation, of both relative binding free energy differences and conformational sampling, demonstrates NBTI's usefulness for free energy calculations in macromolecular simulations.
About this StructureAbout this Structure
2BZA is a Single protein structure of sequence from Bos taurus with , , and as ligands. Active as Trypsin, with EC number 3.4.21.4 Full crystallographic information is available from OCA.
ReferenceReference
Non-Boltzmann thermodynamic integration (NBTI) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine., Ota N, Stroupe C, Ferreira-da-Silva JM, Shah SA, Mares-Guia M, Brunger AT, Proteins. 1999 Dec 1;37(4):641-53. PMID:10651279
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