Effective Use of Empirical Data for Virtual Screening against APJR GPCR Receptor
| Autor: | Laura C. E. Manoliu, Adina L. Milac, Eliza C. Martin, Laurentiu N. Spiridon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Computer science
In silico Pharmaceutical Science Organic chemistry Computational biology Ligands Article Receptors G-Protein-Coupled Analytical Chemistry Hybrid Monte Carlo Structural bioinformatics QD241-441 Biomimetics Drug Discovery Humans Physical and Theoretical Chemistry Throughput (business) Apelin receptor Apelin Receptors Virtual screening Binding Sites structural bioinformatics molecular docking High-Throughput Screening Assays apelin receptor Molecular Docking Simulation Chemistry (miscellaneous) Docking (molecular) Drug Design Ran Alzheimer Apelin Molecular Medicine Peptides Protein Binding |
| Zdroj: | Molecules, Vol 26, Iss 4894, p 4894 (2021) Molecules Volume 26 Issue 16 |
| ISSN: | 1420-3049 |
| Popis: | Alzheimer’s disease is a neurodegenerative disorder incompatible with normal daily activity, affecting one in nine people. One of its potential targets is the apelin receptor (APJR), a G-protein coupled receptor, which presents considerably high expression levels in the central nervous system. In silico studies of APJR drug-like molecule binding are in small numbers while high throughput screenings (HTS) are already sufficiently many to devise efficient drug design strategies. This presents itself as an opportunity to optimize different steps in future large scale virtual screening endeavours. Here, we ran a first stage docking simulation against a library of 95 known binders and 3829 generated decoys in an effort to improve the rescoring stage. We then analyzed receptor binding site structure and ligands binding poses to describe their interactions. As a result, we devised a simple and straightforward virtual screening Stage II filtering score based on search space extension followed by a geometric estimation of the ligand—binding site fitness. Having this score, we used an ensemble of receptors generated by Hamiltonian Monte Carlo simulation and reported the results. The improvements shown herein prove that our ensemble docking protocol is suited for APJR and can be easily extrapolated to other GPCRs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|