MDR SurFlexDock: A Semi-automatic Webserver for Discrete Receptor-Ensemble Docking

Filho, João Luiz de Almeida; Fernández, Jorge Hernández

doi:10.1007/978-3-030-46417-2_4

Cited by 3 publications

(3 citation statements)

References 12 publications

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“…For the SBVS campaign, the enzymes Mpro and RdRp were challenged against ligand database (ZINC15/Enzyme/Trial and ZINC15/Enzyme/World) that have a total of 3,400 molecules already approved by several international regulatory agencies. HTP SurflexDock pipeline uses GROMACS 5.2 ( Abraham et al, 2015 ) for molecular simulations and receptor ensemble sampling and Autodock 4.2 ( Morris et al, 2009 ) for docking experiments ( de Almeida Filho and Fernandez, 2020 ). In the initial HTP SurflexDock scoring results, a functional cut-off of Ki less than 10E-9 kcal/mol were considered as good candidates for re-scoring experiment.…”

Section: Methodsmentioning

confidence: 99%

“…The HTP SurflexDock 1.0 pipeline 4 is based on MDR SurflexDock pipeline ( de Almeida Filho and Fernandez, 2020 ), modified to perform ‘docking and scoring’ experiments to classify promising compounds in SBVS experiments. Thus, we incorporated two types of post-processing analysis into the HTP SurflexDock pipeline: (1) Manual refinement and re-scoring of compounds and (2) Inference of binding free energy (ΔΔG) for most promising complexes using MM/PBSA.…”

Section: Methodsmentioning

confidence: 99%

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Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

et al. 2022

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The COVID-19 pandemic has had an unprecedented impact on the global economy and public health. Its etiologic agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible, pathogenic and has a rapid global spread. Currently, the increase in the number of new confirmed cases has been slowed down due to the increase of vaccination in some regions of the world. Still, the rise of new variants has influenced the detection of additional waves of rising cases that some countries have experienced. Since the virus replication cycle is composed of many distinct stages, some viral proteins related to them, as the main-protease (Mpro) and RNA dependent RNA polymerase (RdRp), constitute individual potential antiviral targets. In this study, we challenged the mentioned enzymes against compounds pre-approved by health regulatory agencies in a virtual screening and later in Molecular Mechanics/Poisson–Bolzmann Surface Area (MM/PBSA) analysis. Our results showed that, among the identified potential drugs with anti-SARS-CoV-2 properties, Hypericin, an important component of the Hypericum perforatum that presents antiviral and antitumoral properties, binds with high affinity to viral Mpro and RdRp. Furthermore, we evaluated the activity of Hypericin anti-SARS-CoV-2 replication in an in vitro model of Vero-E6 infected cells. Therefore, we show that Hypericin inhibited viral replication in a dose dependent manner. Moreover, the cytotoxicity of the compound, in cultured cells, was evaluated, but no significant activity was found. Thus, the results observed in this study indicate that Hypericin is an excellent candidate for repurposing for the treatment of COVID-19, with possible inhibition of two important phases of virus maturation.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

et al. 2022

Self Cite

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“…Based on our previous work [De Almeida Filho and Fernandez 2019], the ensemble docking protocol builds the ensemble from the original receptor structure. Another three conformations are obtained from five nanoseconds MD using Gromacs 5.1.5 [Abraham et al 2015].…”

Section: Platform Descriptionmentioning

confidence: 99%

HTP SurflexDock: a web tool for Structure-Based Virtual Screening analysis based on the Ensemble Docking protocol

Filho¹,

Fernández²

2022

Anais Do XVI Brazilian E-Science Workshop (BRESCI 2022)

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Structure-Based Virtual Screening (SVBS) is a technique traditionally used to find a set of specific inhibitors for a receptor structure during the preliminary stages of drug discovery studies. However, more than 90% of SBVS best ranks compounds do not have the expected biological effect at the end of the process. In this context, strategies to increase the success rate must be employed to ensure the experiment's success. Here, we introduce the HTP SurflexDock, a tool that improves the success rate of SBVS experiments through two strategies: First, the ensemble docking protocol enables the simulation of the implicit flexibility of the receptor structure. Second, a post-processing steps allows the user to rescore promising compounds by expanding the conformational space search or estimating the binding free energy through the MM/PBSA protocol. HTP SurflexDock is useful when dealing with flexible receptors and when structural information about the receptor contact area is insufficient or optimized for a specific ligand type. HTP SurflexDock is freely available as a web service or may be downloaded at https://htpsurflexdock.biocomp.uenf.br/.

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Purification, Structural Characterization, and Anticandidal Activity of a Chitin-Binding Peptide with High Similarity to Hevein and Endochitinase Isolated from Pepper Seeds

Gonçalves,

de Azevedo dos Santos,

da Silva

et al. 2024

Curr Microbiol

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MDR SurFlexDock: A Semi-automatic Webserver for Discrete Receptor-Ensemble Docking

Cited by 3 publications

References 12 publications

Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

Identification of Hypericin as a Candidate Repurposed Therapeutic Agent for COVID-19 and Its Potential Anti-SARS-CoV-2 Activity

HTP SurflexDock: a web tool for Structure-Based Virtual Screening analysis based on the Ensemble Docking protocol

Purification, Structural Characterization, and Anticandidal Activity of a Chitin-Binding Peptide with High Similarity to Hevein and Endochitinase Isolated from Pepper Seeds

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