Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00490170" target="_blank" >RIV/61388963:_____/18:00490170 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/18:00495169 RIV/61989592:15310/18:73591477
Result on the web
<a href="http://dx.doi.org/10.1002/cphc.201701104" target="_blank" >http://dx.doi.org/10.1002/cphc.201701104</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cphc.201701104" target="_blank" >10.1002/cphc.201701104</a>

Result language
angličtina
Original language name
Ranking Power of the SQM/COSMO Scoring Function on Carbonic Anhydrase II-Inhibitor Complexes
Original language description
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 anhydraseII through Zn2+ in the active site. This new dataset consists of the high-resolution (1.1-1.4 angstrom) 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 R-2 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.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10403 - Physical chemistry

Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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