1CE5

BOVINE PANCREAS BETA-TRYPSIN IN COMPLEX WITH BENZAMIDINE

Summary for 1CE5

• Entry DOI: 10.2210/pdb1ce5/pdb
• Descriptor: PROTEIN (TRYPSIN), CALCIUM ION, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: hydrolase (serine proteinase), hydrolase
• Biological source: Bos taurus (cattle)
• Total number of polymer chains: 1
• Total formula weight: 23616.03

Authors

Ota, N.,Stroupe, C.,Ferreira-Da-Silva, J.M.S.,Shah, S.S.,Mares-Guia, M.,Brunger, A.T. (deposition date: 1999-03-16, release date: 1999-03-23, Last modification date: 2024-10-30)

Primary citation

Ota, N.,Stroupe, C.,Ferreira-da-Silva, J.M.,Shah, S.A.,Mares-Guia, M.,Brunger, A.T.
Non-Boltzmann thermodynamic integration (NBTI) for macromolecular systems: relative free energy of binding of trypsin to benzamidine and benzylamine.
Proteins, 37:641-653, 1999

PubMed Abstract: 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.

PubMed: 10651279
DOI: 10.1002/(SICI)1097-0134(19991201)37:4<641::AID-PROT14>3.0.CO;2-W

Experimental method

X-RAY DIFFRACTION (1.9 Å)