• EMILIO MATEEV Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University–Sofia
  • IVA VALKOVA Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University–Sofia
  • MAYA GEORGIEVA Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University–Sofia
  • ALEXANDER ZLATKOV Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University–Sofia



Molecular docking, MAO-B, Ensemble docking, Enrichment factor


Objective: The recent growth of highly resoluted crystallographic structures, together with the continuous improvements of the computing power, has established molecular docking as a leading drug design technique. However, the problems concerning the receptor flexibility and the lowered ability of docking software to correctly score the occurred interactions in some receptors are still relevant.

Methods: Recently, several research groups have reported an enhancement in enrichment values when ensemble docking has been applied. Therefore, we utilized the latest technique for a dataset of Monoamine Oxidase–B (MAO-B) inhibitors. The docking program GOLD 5.3 was used in our study. Several docking parameters (grid space, scoring functions and ligand flexibility) were altered in order to achieve the optimal docking protocol.

Results: The results of 200 000+docking simulations are represented in a modest table. The ensembled simulations demonstrated low ability of the docking software to correctly score the actives seeded in the dataset. However, the superimposed complex-1S3B-1OJA-1OJC, achieved a moderate enrichment value equaled to 9. No significant improvements were noted when five complexed receptors were employed.

Conclusion: As a conclusion, it should be noted that in some cases the ensemble docking enhanced the database enrichments, however overall the value is not suitable for future virtual screening. Further investigations in that area should be considered.


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Pinzi L, Rastelli G. Molecular docking: shifting paradigms in drug discovery. Int J Mol Sci 2019;20:4331.

Sudha R, Kanakam C, Nithya G. Molecular docking studies and bioactivity of various benzilic acids and its analgogs. Asian J Pharm Clin Res 2018;11:463-6.

Awuni Y, Mu Y. Reduction of false positives in structure-based virtual screening when receptor plasticity is considered. Molecules 2015;20:5152-64.

Li J, Fu A, Zhang L. An overview of scoring functions used for protein-ligand interactions in molecular docking. Interdiscip Sci 2019;11:320-8.

Alhossary A, Handoko SD, Mu Y, Kwoh CK. Fast, accurate, and reliable molecular docking with QuickVina 2. Bioinformatics 2015;31:2214-6.

Jeyam M, Karthika G, Poornima V, Sharanya M. Molecular understanding and Insilico validation of traditional medicines for Parkinson's disease. Asian J Pharm Clin Res 2012;5:125-8.

Lovell T, Chen H, Lyne PD, Giordanetto F, Li J. On evaluating molecular-docking methods for pose prediction and enrichment factors. J Chem Inf Model 2006;46:401−15.

Korb O, Olsson TSG, Bowden SJ, Hall RJ, Verdonk ML, Liebeschuetz JW, et al. Potential and limitations of ensemble docking. J Chem Inf Model 2012;52:1262-74.

Craig IR, Essex JW, Spiegel K. Ensemble docking into multiple crystallographically derived protein structures: an evaluation based on the statistical analysis of enrichments. J Chem Inf Model 2010;50:511-24.

Rao S, Sanschagrin PC, Greenwood JR, Repasky MP, Sherman W, Farid R. Improving database enrichment through ensemble docking. J Comput Aided Mol Des 2008;22:621-7.

Binda C, Newton Vinson P, Hubalek F, Edmondson DE, Mattevi A. Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat Struct Biol 2002;9:22-6.

Hubalek F, Binda C, Khalil A, Li M, Mattevi A, Castagnoli N, et al. Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase b by specific reversible inhibitors. J Biol Chem 2005;280:15761-6.

Milczek EM, Binda C, Rovida S, Mattevi A, Edmondson DE. The ‘gating’ residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition. FEBS J 2011;278:4860-9.

Li M, Binda C, Mattevi A, Edmondson DE. Functional role of the aromatic cage in human monoamine oxidase b: structures and catalytic properties of tyr435 mutant proteins. Biochemistry 2006;45:4775-84.

Akyüz MA, Erdem SS, Edmondson DE. The aromatic cage in the active site of monoamine oxidase B: effect on the structural and electronic properties of bound benzylamine and p-nitrobenzylamine. J Neural Transm 2007;114:693-8.

Binda C, Mattevi A, Edmondson DE. Structure-function relationships in flavoenzyme-dependent amine oxidations. J Biol Chem 2002;277:23973-6.

Smith TE, Weissbach H, Udenfriend S. Studies on monoamine oxidase: the mechanism of inhibition of monoamine oxidase by iproniazid. Biochemistry 1963;2:746-51.

Ogidigo J, Anosike CON, Omotuyi O, Oyekanmi N, Metibemu D. In silico molecular docking and pharmacokinetic studies of some selected Phyto-constituents of bryophyllumpinnatum as a potential selective inhibitor of monoamine oxidase–B (MAO-B). Pharmacologyonline 2018;3:272-85.

Liebeschuetz JW, Cole JC, Korb O. Pose prediction and virtual screening performance of GOLD scoring functions in a standardized test. J Comput Aided Des 2012;26:737-48.

Nurisso A, Bravo J, Carrupt PA, Daina A. Molecular docking using the molecular lipophilicity potential as a hydrophobic descriptor: impact on GOLD docking performance. J Chem Inf Model 2012;52:1319-27.

Helen B, Kim H, Namura H. Announcing the worldwide protein data bank. Nat Struct Biol 2003;10:980.

Mysinger MM, Carchia M, Irwin JJ, Shoichet BK. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking. J Med Chem 2012;55:6582-94.

Zhou Z, Felts AK, Friesner RA, Levy RM. Comparative performance of several flexible docking programs and scoring functions: enrichment studies for a diverse set of pharmaceutically relevant targets. J Chem Inf Model 2007;47:1599-608.

Huang SY, Zou X. Ensemble docking of multiple protein structures: considering protein structural variations in molecular docking. Proteins 2007;66:399-421.

Huang SY. Comprehensive assessment of flexible-ligand docking algorithms: current effectiveness and challenges. Brief Bioinform 2018;19:982-94.

Huang SY, Zou X. Advances and challenges in protein-ligand docking. Int J Mol Sci 2010;11:3016-34.



How to Cite

MATEEV, E., I. VALKOVA, M. GEORGIEVA, and A. ZLATKOV. “DATABASE ENRICHMENTS OF MAO-B THROUGH ENSEMBLE DOCKING”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 13, no. 8, Aug. 2021, pp. 32-35, doi:10.22159/ijpps.2021v13i8.41956.



Original Article(s)