5NY6

Carbonic Anhydrase II Inhibitor RA12

Summary for 5NY6

• Entry DOI: 10.2210/pdb5ny6/pdb
• Related: 5NXG 5NXI 5NXM 5NXO 5NXP 5NXV 5NXW 5NY1 5NY3
• Descriptor: Carbonic anhydrase 2, ZINC ION, 4-chloranyl-~{N}-[(1~{R})-1-(2-hydroxyphenyl)ethyl]-3-sulfamoyl-benzamide, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase ii, ca inhibitor, lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29845.81

Authors

Brynda, J.,Rezacova, P.,Horejsi, M.,Fanfrlik, J. (deposition date: 2017-05-11, release date: 2018-01-17, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.1 Å)