4JPU

Crystal structure of Cytochrome C Peroxidase W191G-Gateless in complex with Benzamidine

4JPU の概要

• エントリーDOI: 10.2210/pdb4jpu/pdb
• 関連するPDBエントリー: 1KXM 1KXN 4JM5 4JM6 4JM8 4JM9 4JMA 4JMW 4JPL 4JPT 4JPU 4JQJ 4JQK 4JQM 4JQN
• 分子名称: Cytochrome c peroxidase, PROTOPORPHYRIN IX CONTAINING FE, BENZAMIDINE, ... (5 entities in total)
• 機能のキーワード: model system, ligand binding, free energy calculation, molecular dynamics, oxidoreductase
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33855.16

構造登録者

Boyce, S.E.,Fischer, M.,Fish, I. (登録日: 2013-03-19, 公開日: 2013-07-31, 最終更新日: 2024-02-28)

主引用文献

Rocklin, G.J.,Boyce, S.E.,Fischer, M.,Fish, I.,Mobley, D.L.,Shoichet, B.K.,Dill, K.A.
Blind prediction of charged ligand binding affinities in a model binding site.
J.Mol.Biol., 425:4569-4583, 2013

PubMed Abstract: Predicting absolute protein-ligand binding affinities remains a frontier challenge in ligand discovery and design. This becomes more difficult when ionic interactions are involved because of the large opposing solvation and electrostatic attraction energies. In a blind test, we examined whether alchemical free-energy calculations could predict binding affinities of 14 charged and 5 neutral compounds previously untested as ligands for a cavity binding site in cytochrome c peroxidase. In this simplified site, polar and cationic ligands compete with solvent to interact with a buried aspartate. Predictions were tested by calorimetry, spectroscopy, and crystallography. Of the 15 compounds predicted to bind, 13 were experimentally confirmed, while 4 compounds were false negative predictions. Predictions had a root-mean-square error of 1.95 kcal/mol to the experimental affinities, and predicted poses had an average RMSD of 1.7Å to the crystallographic poses. This test serves as a benchmark for these thermodynamically rigorous calculations at predicting binding affinities for charged compounds and gives insights into the existing sources of error, which are primarily electrostatic interactions inside proteins. Our experiments also provide a useful set of ionic binding affinities in a simplified system for testing new affinity prediction methods.

PubMed: 23896298
DOI: 10.1016/j.jmb.2013.07.030

実験手法

X-RAY DIFFRACTION (1.41 Å)