PDBsum entry 5nxp

Lyase

PDB id: 5nxp

Contents

Protein chain

258 a.a.

Ligands

9DH

Metals

_ZN

Waters ×285

References listed in PDB file

Key reference

• Title: Ranking power of the sqm/cosmo scoring function on carbonic anhydrase ii-Inhibitor complexes.
• Authors: A.Pecina, J.Brynda, L.Vrzal, R.Gnanasekaran, M.Hořejší, S.M.Eyrilmez, J.ŘEzáč, M.Lepšík, P.ŘEzáčová, P.Hobza, P.Majer, V.Veverka, J.Fanfrlík.
• Ref.: Chemphyschem, 2018, 19, 873-879. [DOI no: 10.1002/cphc.201701104]
• PubMed id: 29316128

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 Zn²⁺ 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_i ) 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 R² 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.