Multi-structure docking analysis of BACE1 crystal structures and non-peptidic ligands
| Autor: | Ramin Miri, Bahram Hemmateenejad, Zahra Haghighijoo, Najmeh Edraki, Saeed Emami |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Computer science Protein Data Bank (RCSB PDB) Computational biology Ligands Chemometrics Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine mental disorders Materials Chemistry Aspartic Acid Endopeptidases Cluster Analysis Protease Inhibitors Physical and Theoretical Chemistry Spectroscopy Lead Finder Crystallography Molecular Structure Linear discriminant analysis Computer Graphics and Computer-Aided Design Combinatorial chemistry Molecular Docking Simulation 030104 developmental biology Protein–ligand docking Searching the conformational space for docking Docking (molecular) Principal component analysis Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery |
| Zdroj: | Journal of Molecular Graphics and Modelling. 76:128-135 |
| ISSN: | 1093-3263 |
| DOI: | 10.1016/j.jmgm.2017.06.023 |
| Popis: | In order to design novel non-peptidic inhibitors of BACE1, many research groups have attempted using computational studies including docking analyses. Since there are too many 3D structures for BACE1 in the protein database, the selection of suitable crystal structures is a key prerequisite for the successful application of molecular docking. We employed a multi-structure docking protocol. In which 615 ligands' structures were docked into 150 BACE1 structures. The large number of the resultant docking scores were post-processed by different data analysis methods including exploratory data analysis, regression analysis and discriminant analysis. It was found that using one crystal structure for docking did not result in high accuracy for predicting activity of the BACE1 inhibitors. Instead, using of the multi-structural docking scores, post-processed by chemometrics methods arrived to highly accurate predictive models. In this regards, the PDB accession codes of 4B70, 4DVF and 2WEZ could discriminate between active and inactive compounds, with higher accuracy. Clustering of the BACE1 structures based on principal component analysis of the crystallographic structures the revealed that the discriminant structures are in the center of the clusters. Thus, these structures can be selected as predominant crystal structures for docking studies of non-peptidic BACE1 inhibitors. |
| Databáze: | OpenAIRE |
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