Naslov
Evaluation of scoring functions use in case of acetylcholinesterase inhibitors

Autori
Šinko, Goran ; Maraković, Nikola

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Molecular Medicine and Biotechnology, International symposium at 40th anniversary of Institute of Biochemistry and 20th anniversary of Medical Centre for Molecular Biology, Ljubljana, Slovenija, Book of Abstracts / Hudler, Petra ; Videtič Paska, Alja ; Juvan, Peter - Ljubljana : Birografika BORI d.o.o., 2012

ISBN
978-961-267-050-4

Skup
Molecular Medicine and Biotechnology, International symposium at 40th anniversary of Institute of Biochemistry and 20th anniversary of Medical Centre for Molecular Biology

Mjesto i datum
Ljubljana, Slovenija, 27.06.2012. - 29.06.2012

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
molecular modelling; receptor-ligand interactions; scoring functions

Sažetak
Introduction: Molecular modelling tools are recognised as helpful in a drug design and medicinal chemistry. Proper evaluation of receptor-ligand interaction is main goal in drug design and development. Next step will be a prediction of receptor-ligand interaction with respect to affinity, required for a ligand structure optimization. Recognition of key interactions is beneficial for developing selective and high affinity ligands. Scoring functions are introduced for this purpose. They are developed by correlating interactions from numerous crystal structures of various different receptor-ligand complexes with matching inhibition constant. Results: Here we evaluated several high affinity acetylcholinesterase inhibitors using scoring functions to determine correlation between reported inhibition constant for following inhibitor complexes PDB ID: 1E66, 1EVE, 1H22, 1H23, 1U65, 1ZGB and 1ZGC, and score values derived from scoring functions. We used following scoring functions available in Accelrys DiscoveryStudio software: PLP1, PLP2 [1], PMF, PMF04 [2], Jain [3], LigScore1 and LigScore2 [4]. Deviation between inhibition constants was 10% while deviation between matching scores were from 12 to 40%. Conclusions: Scoring function LigScore2 and PLP2 evaluated well acetylcholinesterase-inhibitor complexes with lowest score deviation. Although LigScore2 predicted logarithmic value of affinity in two cases (1H23 and 1ZGC), some disagreement was noticed due to 25% lower value of predicted affinities. References: 1. Gehlhaar DK, et al. (1995) Chem. Biol. 2, 317-24. 2. Muegge I, (2006) J. Med. Chem. 49(20), 5895-5902. 3. Jain AN, (1996) J. Comput.-Aided Mol. Design 10, 427-440. 4. Krammer A, et al. (2005) J. Mol. Graph. Model. 23, 395-407.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA