1CE5

BOVINE PANCREAS BETA-TRYPSIN IN COMPLEX WITH BENZAMIDINE

1CE5 の概要

• エントリーDOI: 10.2210/pdb1ce5/pdb
• 分子名称: PROTEIN (TRYPSIN), CALCIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase (serine proteinase), hydrolase
• 由来する生物種: Bos taurus (cattle)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23616.03

構造登録者

Ota, N.,Stroupe, C.,Ferreira-Da-Silva, J.M.S.,Shah, S.S.,Mares-Guia, M.,Brunger, A.T. (登録日: 1999-03-16, 公開日: 1999-03-23, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.9 Å)