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PDBsum entry 1ce5
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Non-Boltzmann thermodynamic integration (nbti) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine.
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Authors
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N.Ota,
C.Stroupe,
J.M.Ferreira-Da-Silva,
S.A.Shah,
M.Mares-Guia,
A.T.Brunger.
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Ref.
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Proteins, 1999,
37,
641-653.
[DOI no: ]
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PubMed id
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Abstract
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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.
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Figure 2.
Figure 2. The change in charges and covalent geometry for the
mutation form benzamidine (BZD) to benzylamine (BZA). Dm
indicates a dummy atom and C7 of BZD is located at the center of
the spherical boundary method.
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Figure 4.
Figure 4. Comparison of the binding pocket of crystal
structures of trypsin-inhibitor complexes. Superposition of the
trypsin-BZA complex (green) onto the trypsin-BZD complex
(magenta) using the Ca atoms of trypsin of the reservoir region.
The side chain of Gln 192 is not shown because of multiple
conformations.
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The above figures are
reprinted
by permission from John Wiley & Sons, Inc.:
Proteins
(1999,
37,
641-653)
copyright 1999.
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Secondary reference #1
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Title
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Crystal structure of bovine beta-Trypsin at 1.5 a resolution in a crystal form with low molecular packing density. Active site geometry, Ion pairs and solvent structure.
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Authors
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H.D.Bartunik,
L.J.Summers,
H.H.Bartsch.
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Ref.
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J Mol Biol, 1989,
210,
813-828.
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PubMed id
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Secondary reference #2
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Title
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The geometry of the reactive site and of the peptide groups in trypsin, Trypsinogen and its complexes with inhibitors
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Authors
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M.Marquart,
J.Walter,
J.Deisenhofer,
W.Bode,
R.Huber.
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Ref.
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acta crystallogr ,sect b, 1983,
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480.
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