Use of Molecular Docking as a Decision-Making Tool in Drug Discovery

Abdolmaleki, Azizeh; Shiri, Fereshteh; Ghasemi, Jahan B.

doi:10.1016/b978-0-12-822312-3.00010-2

Cited by 13 publications

(8 citation statements)

References 71 publications

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“…The biochemical interactions in molecular docking simulation are to be modeled to guess where and how molecules bind to each other. The results of large‐scale molecular docking simulations can offer valuable insight into the relationship between a ligand and a receptor 19 . This useful method can be used in biomedical research before performing in vivo or in vitro tests.…”

Section: Methodsmentioning

confidence: 99%

The in vitro apoptotic effect of new zinc complex possessing folic acid and phenanthroline on cervix cancer cells

Yang

Majd

Shiri

et al. 2021

Applied Organom Chemis

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With proper care and nursing as well as timely diagnosis and good treatment, cervical cancer is one of the most treatable forms of cancer. One of the most important cancer treatments is the use of emerging developing metal–organic complexes, which can provide a wide variety of morphologies, sizes, and properties based on different metal ions and different organic ligands. Accordingly, we reported the synthesis method, structural properties, cytotoxicity, apoptotic properties, and molecular docking analysis of the new Zn(II) complex consisting of phenanthroline and folic acid ligands. FTIR, 1H‐NMR, 13C‐NMR, and elemental analyzer determined that the synthesis of the complex was successful. The IC50 values (380 and 199 μM) were shown that the viability of HeLa cells was dependent on time of exposure and concentration of [Zn(Phen)FA] complex. Real‐time PCR clearly shows increased expression of apoptotic genes in cervical carcinoma HeLa cells and a possible relationship between Bak1/Bclx ratio and caspase‐3. Also, the key amino acids of folate receptor that can interact with the synthesized complex were identified by molecular docking analysis. Moreover, molecular electrostatic potential confirmed that carboxylate portion of FA is an electron‐rich region and can interact with Zn(Phen) to form a stable and soluble complex. All experiments confirmed that presence of FA could improve stability, cytotoxicity, apoptosis, and cellular uptake of complex in cervical carcinoma HeLa cells.

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Section: Methodsmentioning

confidence: 99%

The in vitro apoptotic effect of new zinc complex possessing folic acid and phenanthroline on cervix cancer cells

Yang

Majd

Shiri

et al. 2021

Applied Organom Chemis

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“…Glide standard precision mode and AutodockVina are used for docking, and top ligand poses were retained for structural refinements. 46,47 Both sites' three ligands were docked, and the scores were tabulated. 44,48…”

Section: Molecular Modeling and Dockingmentioning

confidence: 99%

Structural analysis of human G‐protein‐coupled receptor 17 ligand binding sites

Mani

Ramesh

Yli‐Harja

et al. 2023

J of Cellular Biochemistry

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The human G protein coupled membrane receptor (GPR17), the sensor of brain damage, is identified as a biomarker for many neurological diseases. In human brain tissue, GPR17 exist in two isoforms, long and short. While cryo‐electron microscopy technology has provided the structure of the long isoform of GPR17 with Gi complex, the structure of the short isoform and its activation mechanism remains unclear. Recently, we theoretically modeled the structure of the short isoform of GPR17 with Gi signaling protein and identified novel ligands. In the present work, we demonstrated the presence of two distinct ligand binding sites in the short isoform of GPR17. The molecular docking of GPR17 with endogenous (UDP) and synthetic ligands (T0510.3657, MDL29950) found the presence of two distinct binding pockets. Our observations revealed that endogenous ligand UDP can bind stronger in two different binding pockets as evidenced by glide and autodock vina scores, whereas the other two ligand's binding with GPR17 has less docking score. The analysis of receptor−UDP interactions shows complexes' stability in the lipid environment by 100 ns atomic molecular dynamics simulations. The amino acid residues VAL83, ARG87, and PHE111 constitute ligand binding site 1, whereas site 2 constitutes ASN67, ARG129, and LYS232. Root mean square fluctuation analysis showed the residues 83, 87, and 232 with higher fluctuations during molecular dynamics simulation in both binding pockets. Our findings imply that the residues of GPR17's two binding sites are crucial, and their interaction with UDP reveals the protein's hidden signaling and communication properties. Furthermore, this finding may assist in the development of targeted therapies for the treatment of neurological diseases.

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“…Moreover, a well‐known in silico structure‐based technique utilized extensively in drug development is molecular docking. Without knowing in advance, the chemical makeup of other target modulators, docking makes it possible to find novel therapeutic compounds, anticipate ligand–target interactions at the molecular level, or define structure–activity connections (Abdolmaleki et al, 2021; Pinzi & Rastelli, 2019; Wang & Zhu, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Without knowing in advance, the chemical makeup of other target modulators, docking makes it possible to find novel therapeutic compounds, anticipate ligand-target interactions at the molecular level, or define F I G U R E 1 Some known acetic acid derivatives as aldose reductase inhibitors. structure-activity connections (Abdolmaleki et al, 2021;Pinzi & Rastelli, 2019;Wang & Zhu, 2016). Some known ARIs such as zanarestat, ponalrestat, and zopolrestat contain both quinazoline isomers and acetic acid moiety (Figure 1).…”

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confidence: 99%

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

Tokalı

Demir

Türkeş

et al. 2023

Drug Development Research

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Aldose reductase (AR) is a crucial enzyme of the polyol pathway through which glucose is metabolized under conditions of hyperglycemia related to diabetes. A series of novel acetic acid derivatives containing quinazolin-4(3H)-one ring (1-22) was synthesized and tested for in vitro AR inhibitory effect. All the target compounds exhibited nanomolar activity against the target enzyme, and all compounds displayed higher activity as compared to the reference drug epalrestat.Among them, Compound 19, named 2-(4-[(2-[(4-methylpiperazin-1-yl)methyl]-4oxoquinazolin-3(4H)-ylimino)methyl]phenoxy)acetic acid, displayed the strongest inhibitory effect with a K I value of 61.20 ± 10.18 nM. Additionally, these compounds were investigated for activity against L929, nontumoral fibroblast cells, and MCF-7, breast cancer cells using the MTT assay. Compounds 16 and 19 showed lower toxicity against the normal L929 cells. The synthesized compounds' (1-22) absorption, distribution, metabolism, and excretion properties were also evaluated.Molecular docking simulations were used to look into the possible binding mechanisms of these inhibitors against AR.

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Use of Molecular Docking as a Decision-Making Tool in Drug Discovery

Cited by 13 publications

References 71 publications

The in vitro apoptotic effect of new zinc complex possessing folic acid and phenanthroline on cervix cancer cells

The in vitro apoptotic effect of new zinc complex possessing folic acid and phenanthroline on cervix cancer cells

Structural analysis of human G‐protein‐coupled receptor 17 ligand binding sites

Novel acetic acid derivatives containing quinazolin‐4(3H)‐one ring: Synthesis, in vitro, and in silico evaluation of potent aldose reductase inhibitors

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