Molecular Docking: Shifting Paradigms in Drug Discovery

Pinzi, Luca; Rastelli, Giulio

doi:10.3390/ijms20184331

Cited by 1,277 publications

(831 citation statements)

References 205 publications

(367 reference statements)

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“…Hence, besides monitoring the dynamic equilibration of the TRPM8 tetramer, the MD run was also utilized as a valuable source of multiple receptor conformations to be used in the following docking simulations [21]. In detail, the frames were selected based on their similarity with the resolved structures in complex with icilin and WS-12 [19].…”

Section: Introductionmentioning

confidence: 99%

Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on the hTRPM8 Channel

Talarico

Gervasoni

Manelfi

et al. 2020

IJMS

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Background: There is an increasing interest in TRPM8 ligands of medicinal interest, the rational design of which can be nowadays supported by structure-based in silico studies based on the recently resolved TRPM8 structures. Methods: The study involves the generation of a reliable hTRPM8 homology model, the reliability of which was assessed by a 1.0 μs MD simulation which was also used to generate multiple receptor conformations for the following structure-based virtual screening (VS) campaigns; docking simulations utilized different programs and involved all monomers of the selected frames; the so computed docking scores were combined by consensus approaches based on the EFO algorithm. Results: The obtained models revealed very satisfactory performances; LiGen™ provided the best results among the tested docking programs; the combination of docking results from the four monomers elicited a markedly beneficial effect on the computed consensus models. Conclusions: The generated hTRPM8 model appears to be amenable for successful structure-based VS studies; cross-talk modulating effects between interacting monomers on the binding sites can be accounted for by combining docking simulations as performed on all the monomers; this strategy can have general applicability for docking simulations involving quaternary protein structures with multiple identical binding pockets.

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Section: Introductionmentioning

confidence: 99%

Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on the hTRPM8 Channel

Talarico

Gervasoni

Manelfi

et al. 2020

IJMS

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“…In the past few years, network pharmacology, as a new discipline based on system biology and multi-direction pharmacology, can effectively implement the predictive analysis of drug action mechanisms [25], identify new drug targets [26], and better explain the mechanism of interactions between bioactive molecules and cellular pathways. Molecular docking technology is an advantageous tool for modernization research and can achieve virtual screening of drugs [27]. Reverse molecular docking refers to the docking of a small molecule drug in a group of potential binding cavities of clinically relevant large molecule targets.…”

Section: Introductionmentioning

confidence: 99%

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

Lin

et al. 2020

Preprint

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Background: It has been demonstrated that fucosterol induces a therapeutic effect on cancer. However, the molecular mechanisms underlying the effects of fucosterol in the treatment of non-small cell lung cancer are still unclear.Methods: In this study, pharmMapper and GeneCards databases were utilized to gather the prediction of fucosterol targets and NSCLC-related targets. The mechanisms of fucosterol against NSCLC were identified in DAVID6.8 by enrichment analysis of GO and KEGG, and protein-protein interaction data was obtained from Sting Database. Molecular docking was used to predict the docking of GRB2. Moreover, the relationship of GRB2 expression and immune infiltrates was analyzed by TIMER database.Results: The results suggest that fucosterol acts against by candidate targets, such as MAPK1, EGFR, GRB2, IGF2, MAPK8 and SRC, which regulate biological processes including negative regulation of apoptotic process, peptidyl-tyrosine phosphorylation, positive regulation of cell proliferation. The Raf / MEK / ERK signaling pathway initiated by GRB2 maybe the most significant pathway for fucosterol to treat NSCLC.Conclusions: These results show that GRB2 is the key target for fucosterol in the treatment of NSCLC, which laying a theoretical foundation for further research and providing scientific support for the development of new drugs.

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“…Besides, molecular docking is a computational method for predicting the placement of ligands in the binding sites of their receptors. It has been widely used in drug discovery [21]. Oxygen-glucose deprivation(OGD/R) cell modelhas been well recognized for stroke in vitro.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rc Protects Neurons From Oxygen-glucose Deprivation Injuries and Its Mechanistic Investigation via a Network Pharmacology-based Analysis

Huang

Chen

Zheng

et al. 2020

Preprint

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Background: Ginsenoside Rc (Rc) is one of the major active components of Panax ginseng Meyer. Studies have shown that Rc has remarkable effect in protection of nervous system. However, the potential molecular mechanism of its neuroprotective effect remains unclear. Our study aim to investigate the neuroprotective effect of Rc on neuron damage and explore the potential mechanism on its regulation of TNF-α and DRP-1.Methods: Oxygen-glucose deprivation reperfusion (OGD/R) cell neuron damage modle was induced by Na2S2O4 and EBSS solution. After preventive administration, cell viability and cell toxicity were detected to evaluate the putative neuroprotective properties of Rc. Network pharmacology and molecular docking simulation studies were performed to predict the potential targets and pharmacological mechanism. Furthermore, the prediction was validated via western blot assay and specific antagonist. Results: In OGD/R injured cells, Rc significantly improved cell viability (Rc middle dose vs. OGD/R model: 67.3±2.33% vs. 55.7±1.14%, P<0.05) and obviously decreased cell toxicity (Rc middle dose vs. OGD/R model: 147±39.7% vs. 232±29.4%, P<0.01). Analysis of network pharmacology and molecular docking indicated that the key targets of Rc are TNF-α and DRP-1. Subsequently molecular biological studies showed a significant increase on expression of TNF-α and DRP-1 in model group. Conversely, administration of Rc reversed the alteration significantly and presented a dose dependence. By adding antagonist, we validated that Rc had an indirect regulation on TNF-α and DRP-1. Conclusions: Rc possess protective properties against OGD-induced neuron damage by regulating the expression of TNF-α and DRP-1.

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Molecular Docking: Shifting Paradigms in Drug Discovery

Cited by 1,277 publications

References 205 publications

Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on the hTRPM8 Channel

Combining Molecular Dynamics and Docking Simulations to Develop Targeted Protocols for Performing Optimized Virtual Screening Campaigns on the hTRPM8 Channel

Exploration in the mechanism of fucosterol for the treatment of non-small cell lung cancer Based on network pharmacology and molecular docking

Ginsenoside Rc Protects Neurons From Oxygen-glucose Deprivation Injuries and Its Mechanistic Investigation via a Network Pharmacology-based Analysis

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