5NYA

Carbonic Anhydrase II Inhibitor RA13

5NYA の概要

• エントリーDOI: 10.2210/pdb5nya/pdb
• 関連するPDBエントリー: 5NXG 5NXI 5NXM 5NXO 5NXP 5NXV 5NXW 5NY1 5NY3 5NY6
• 分子名称: Carbonic anhydrase 2, ZINC ION, benzenesulfonamide, ... (5 entities in total)
• 機能のキーワード: carbonic anhydrase ii, ca inhibitor, lyase
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29287.35

構造登録者

Brynda, J.,Rezacova, P.,Horejsi, M.,Fanfrlik, J. (登録日: 2017-05-11, 公開日: 2018-01-17, 最終更新日: 2024-01-17)

主引用文献

Pecina, A.,Brynda, J.,Vrzal, L.,Gnanasekaran, R.,Horejsi, M.,Eyrilmez, S.M.,Rezac, J.,Lepsik, M.,Rezacova, P.,Hobza, P.,Majer, P.,Veverka, V.,Fanfrlik, J.
Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes.
Chemphyschem, 19:873-879, 2018

PubMed Abstract: Accurate prediction of protein-ligand binding affinities is essential for hit-to-lead optimization and virtual screening. The reliability of scoring functions can be improved by including quantum effects. Here, we demonstrate the ranking power of the semiempirical quantum mechanics (SQM)/implicit solvent (COSMO) scoring function by using a challenging set of 10 inhibitors binding to carbonic anhydrase II through Zn in the active site. This new dataset consists of the high-resolution (1.1-1.4 Å) crystal structures and experimentally determined inhibitory constant (K ) values. It allows for evaluation of the common approximations, such as representing the solvent implicitly or by using a single target conformation combined with a set of ligand docking poses. SQM/COSMO attained a good correlation of R of 0.56-0.77 with the experimental inhibitory activities, benefiting from careful handling of both noncovalent interactions (e.g. charge transfer) and solvation. This proof-of-concept study of SQM/COSMO ranking for metalloprotein-ligand systems demonstrates its potential for hit-to-lead applications.

PubMed: 29316128
DOI: 10.1002/cphc.201701104

実験手法

X-RAY DIFFRACTION (1.2 Å)