LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 19

Search options

  1. Article ; Online: Elucidating structural variability in p53 conformers using combinatorial refinement strategies and molecular dynamics.

    Parves, Md Rimon / Solares, Maria J / Dearnaley, William J / Kelly, Deborah F

    Cancer biology & therapy

    2023  Volume 25, Issue 1, Page(s) 2290732

    Abstract: Low molecular weight proteins and protein assemblies can now be investigated using cryo-electron microscopy (EM) as a complement to traditional structural biology techniques. It is important, however, to not lose sight of the dynamic information inherent ...

    Abstract Low molecular weight proteins and protein assemblies can now be investigated using cryo-electron microscopy (EM) as a complement to traditional structural biology techniques. It is important, however, to not lose sight of the dynamic information inherent in macromolecules that give rise to their exquisite functionality. As computational methods continue to advance the field of biomedical imaging, so must strategies to resolve the minute details of disease-related entities. Here, we employed combinatorial modeling approaches to assess flexible properties among low molecular weight proteins (~100 kDa or less). Through a blend of rigid body refinement and simulated annealing, we determined new hidden conformations for wild type p53 monomer and dimer forms. Structures for both states converged to yield new conformers, each revealing good stereochemistry and dynamic information about the protein. Based on these insights, we identified fluid parts of p53 that complement the stable central core of the protein responsible for engaging DNA. Molecular dynamics simulations corroborated the modeling results and helped pinpoint the more flexible residues in wild type p53. Overall, the new computational methods may be used to shed light on other small protein features in a vast ensemble of structural data that cannot be easily delineated by other algorithms.
    MeSH term(s) Humans ; Molecular Dynamics Simulation ; Cryoelectron Microscopy/methods ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Tumor Suppressor Protein p53
    Language English
    Publishing date 2023-12-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2146305-0
    ISSN 1555-8576 ; 1538-4047
    ISSN (online) 1555-8576
    ISSN 1538-4047
    DOI 10.1080/15384047.2023.2290732
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 5887: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Molecular dynamics-based insight of VEGFR-2 kinase domain: a combined study of pharmacophore modeling and molecular docking and dynamics

    Parves, Md. Rimon / Riza, Yasir Mohamed / Alam, Sanjida / Jaman, Sadia

    J Mol Model. 2023 Jan., v. 29, no. 1 p.17-17

    2023  

    Abstract: BACKGROUND: Inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase by small molecules has become a promising target in the treatment of cancer. OBJECTIVE: In this study, we approached pharmacophore modeling coupled with a ... ...

    Abstract BACKGROUND: Inhibition of vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase by small molecules has become a promising target in the treatment of cancer. OBJECTIVE: In this study, we approached pharmacophore modeling coupled with a structure-based virtual screening workflow to identify the potent inhibitors. METHODS: The top selected hit compounds have been rescored using the MM/GBSA approach. To understand the molecular reactivity, electronic properties, and stability of those inhibitors, we have employed density functional theory and molecular dynamics. Following that, the best 21 hit compounds have been further post-processed with a Quantum ligand partial charge-based rescoring process and further validated by implementing molecular dynamics simulation. RESULTS: The ten hit compounds have been hypothesized and considered as potent inhibitors of VEGFR-2 tyrosine kinase. This study also signifies the contribution of QM-based ligand partial charge, which is more accurate in predicting reliable free binding energy and filtering large ligand libraries to hit optimization, rather than assigning those of the force field-based method. From the binding pattern analysis of all the complexes, amino acids, such as Glu885, Cys919, Cys1045, Thr916, Thr919, and Asp1046, were found to have comprehensive interaction with the hit compounds. CONCLUSION: Hence, this could prove to be useful as a potential inhibition site of the VEGFR-2 tyrosine kinase domain for future researchers. Moreover, this study also emphasizes the conformational changes upon ATP binding, based on either the receptor’s rigidity or flexibility.
    Keywords density functional theory ; energy ; ligands ; models ; molecular dynamics ; pharmacology ; tyrosine ; vascular endothelial growth factor receptor-2
    Language English
    Dates of publication 2023-01
    Size p. 17.
    Publishing place Springer Berlin Heidelberg
    Document type Article ; Online
    ZDB-ID 1284729-X
    ISSN 0948-5023 ; 1610-2940
    ISSN (online) 0948-5023
    ISSN 1610-2940
    DOI 10.1007/s00894-022-05427-x
    Database NAL-Catalogue (AGRICOLA)

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Structural and functional effects of the L84S mutant in the SARS-COV-2 ORF8 dimer based on microsecond molecular dynamics study.

    Islam, Shafiqul / Parves, Md Rimon / Islam, Md Jahirul / Ali, Md Ackas / Efaz, Faiyaz Md / Hossain, Md Shahadat / Ullah, M Obayed / Halim, Mohammad A

    Journal of biomolecular structure & dynamics

    2023  , Page(s) 1–18

    Abstract: The L84S mutation has been observed frequently in the ORF8 protein of SARS-CoV-2, which is an accessory protein involved in various important functions such as virus propagation, pathogenesis, and evading the immune response. However, the specific ... ...

    Abstract The L84S mutation has been observed frequently in the ORF8 protein of SARS-CoV-2, which is an accessory protein involved in various important functions such as virus propagation, pathogenesis, and evading the immune response. However, the specific effects of this mutation on the dimeric structure of ORF8 and its impacts on interactions with host components and immune responses are not well understood. In this study, we performed one microsecond molecular dynamics (MD) simulation and analyzed the dimeric behavior of the L84S and L84A mutants in comparison to the native protein. The MD simulations revealed that both mutations caused changes in the conformation of the ORF8 dimer, influenced protein folding mechanisms, and affected the overall structural stability. In particular, the
    Language English
    Publishing date 2023-07-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2023.2228919
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article: Quantum chemical calculation and binding modes of H1R; a combined study of molecular docking and DFT for suggesting therapeutically potent H1R antagonist.

    Riza, Yasir Mohamed / Parves, Md Rimon / Tithi, Fahmida Alam / Alam, Sanjida

    In silico pharmacology

    2019  Volume 7, Issue 1, Page(s) 1

    Abstract: Histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediates allergies and other pathophysiological diseases. For alleviation of allergic symptoms, H1R antagonists are therapeutic drugs; ... ...

    Abstract Histamine-1 receptor (H1R) belongs to the family of rhodopsin-like G-protein-coupled receptors expressed in cells that mediates allergies and other pathophysiological diseases. For alleviation of allergic symptoms, H1R antagonists are therapeutic drugs; of which the most frequently prescribed are second generation drugs, such as; Cetirizine, Loratadine, Hydroxyzine, Desloratadine, Bepotastine, Acrivastine and Rupatadine. To understand their potency, binding affinity and interaction; we have employed molecular docking and quantum chemical study such as; Induced-fit docking and calculation of quantum chemical descriptors. This study also introduces the binding site characterization of H1R, with its known antagonists and Curcumin (our proposed alternative H1R antagonist); useful for future drug target site. The interactive binding site residues of H1R are found to be; Lys-191, Tyr-108, Asp-107, Tyr-100, Lys-179, Lys-191, Thr-194, Trp-428, Phe-432, Tyr-458, Hie-450, with most of these shown to be inhibited by naturally-occurring compound curcumin. Amongst the FDA approved drugs, Hydroxyzine showed best ligand binding affinity, calculated as - 141.491 kcal/mol and naturally occurring compound, Curcumin showed binding affinity of - 87.046 kcal/mol. The known antagonists of H1R has been used for hypothesizing curcumin as naturally occurring lead compound for the target using accurate molecular docking simulation study. Though the pharmacological action of known inhibitor is already established, they could differ from their reactivity, which we have also focused in our study for predicting drug reactivity.
    Language English
    Publishing date 2019-02-25
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2702993-1
    ISSN 2193-9616
    ISSN 2193-9616
    DOI 10.1007/s40203-019-0050-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Assessment of structurally and functionally high-risk nsSNPs impacts on human bone morphogenetic protein receptor type IA (BMPR1A) by computational approach.

    Islam, Md Jahirul / Parves, Md Rimon / Mahmud, Shafi / Tithi, Fahmida Alam / Reza, Md Abu

    Computational biology and chemistry

    2019  Volume 80, Page(s) 31–45

    Abstract: BMPR1A (BMP type 1 receptor) is a transmembrane cell-surface receptor also known as ALK3 (activin-like kinases-3) encodes for a type I serine/threonine kinase receptor and a member of the transforming growth-factor β-receptor (TGF-β) super family. The ... ...

    Abstract BMPR1A (BMP type 1 receptor) is a transmembrane cell-surface receptor also known as ALK3 (activin-like kinases-3) encodes for a type I serine/threonine kinase receptor and a member of the transforming growth-factor β-receptor (TGF-β) super family. The BMPR1A has a significant interaction with BMP-2 for protein activity and also has a low affinity with growth and differentiation factor 5 (GDF5); positively regulates chondrocyte differentiation. The genetic variations can alter the structure and function of the BMPR1A gene that causes several diseases such as juvenile polyposis syndrome or hereditary cancer-predisposing syndrome. The current study was carried out to identify potential deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in BMPR1A by implementing different computational algorithms such as SIFT, PolyPhen2, SNAP2, PROVEAN, PhD-SNP, SNPs&GO, nsSNPAnalyzer, and P-Mut. From 205 nsSNPs in BMPR1A, 7 nsSNPs (C76Y, C124R, C124Y, C376Y, R443C, R480W, and W487R) were predicted as deleterious in 8 prediction algorithms. The Consurf analysis showed that selected 7 nsSNPs were present in the highly conserved regions. Molecular dynamics simulation analysis also performed to explore conformational changes in the variant structure with respect to its native structure. According to the MDS result, all variants flexibility and rigidity were unbalanced, which may alter the structural and functional behavior of the native protein. Although, three nsSNPs i.e., C124R, C376Y, and R443C have already been reported in patients associated with JPS, but their structural and functional molecular studies remain uncharacterized. Therefore, the findings of this study can provide a better understanding of uncharacterized nsSNPS and to find their association with disease susceptibility and also facilitate to the researchers for designing or developing the target dependent drugs.
    MeSH term(s) Algorithms ; Amino Acid Sequence ; Amino Acid Substitution ; Binding Sites/genetics ; Bone Morphogenetic Protein Receptors, Type I/genetics ; Computational Biology/methods ; Humans ; Hydrogen Bonding ; Molecular Dynamics Simulation ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Protein Conformation, alpha-Helical/genetics ; Protein Stability ; Software
    Chemical Substances BMPR1A protein, human (EC 2.7.11.30) ; Bone Morphogenetic Protein Receptors, Type I (EC 2.7.11.30)
    Language English
    Publishing date 2019-03-12
    Publishing country England
    Document type Journal Article
    ISSN 1476-928X
    ISSN (online) 1476-928X
    DOI 10.1016/j.compbiolchem.2019.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Prediction of Deleterious Non-synonymous SNPs of Human STK11 Gene by Combining Algorithms, Molecular Docking, and Molecular Dynamics Simulation.

    Islam, Md Jahirul / Khan, Akib Mahmud / Parves, Md Rimon / Hossain, Md Nayeem / Halim, Mohammad A

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 16426

    Abstract: Serine-threonine kinase11 (STK11) is a tumor suppressor gene which plays a key role in regulating cell growth and apoptosis. It is widely known as a multitasking kinase and engaged in cell polarity, cell cycle arrest, chromatin remodeling, energy ... ...

    Abstract Serine-threonine kinase11 (STK11) is a tumor suppressor gene which plays a key role in regulating cell growth and apoptosis. It is widely known as a multitasking kinase and engaged in cell polarity, cell cycle arrest, chromatin remodeling, energy metabolism, and Wnt signaling. The substitutions of single amino acids in highly conserved regions of the STK11 protein are associated with Peutz-Jeghers syndrome (PJS), which is an autosomal dominant inherited disorder. The abnormal function of the STK11 protein is still not well understood. In this study, we classified disease susceptible single nucleotide polymorphisms (SNPs) in STK11 by using different computational algorithms. We identified the deleterious nsSNPs, constructed mutant protein structures, and evaluated the impact of mutation by employing molecular docking and molecular dynamics analysis. Our results show that W239R and W308C variants are likely to be highly deleterious mutations found in the catalytic kinase domain, which may destabilize structure and disrupt the activation of the STK11 protein as well as reduce its catalytic efficiency. The W239R mutant is likely to have a greater impact on destabilizing the protein structure compared to the W308C mutant. In conclusion, these mutants can help to further realize the large pool of disease susceptibilities linked with catalytic kinase domain activation of STK11 and assist to develop an effective drug for associated diseases.
    MeSH term(s) AMP-Activated Protein Kinase Kinases ; Algorithms ; Amino Acid Sequence ; Binding Sites ; Computational Biology/methods ; Humans ; Molecular Conformation ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Molecular Sequence Annotation ; Mutation ; Open Reading Frames ; Polymorphism, Single Nucleotide ; Protein Binding ; Protein Serine-Threonine Kinases/chemistry ; Protein Serine-Threonine Kinases/genetics ; Structure-Activity Relationship ; Untranslated Regions
    Chemical Substances Untranslated Regions ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; STK11 protein, human (EC 2.7.11.1) ; AMP-Activated Protein Kinase Kinases (EC 2.7.11.3)
    Language English
    Publishing date 2019-11-11
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-52308-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: Repurposing fusion inhibitor peptide against SARS-CoV-2.

    Efaz, Faiyaz Md / Islam, Shafiqul / Talukder, Shafi Ahmad / Akter, Shaila / Tashrif, Md Zakaria / Ali, Md Ackas / Sufian, Md Abu / Parves, Md Rimon / Islam, Md Jahirul / Halim, Mohammad A

    Journal of computational chemistry

    2021  Volume 42, Issue 32, Page(s) 2283–2293

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously evolving. Although several vaccines were approved, this pandemic is still a major threat to public life. Till date, no established therapies are available against SARS-CoV-2. Peptide inhibitors hold great promise for this viral pathogen due to their efficacy, safety, and specificity. In this study, seventeen antiviral peptides which were known to inhibit SARS-CoV-1 are collected and computationally screened against heptad repeat 1 (HR1) of the SARS-CoV-2 spike protein (S2). Out of 17 peptides, Fp13 and Fp14 showed better binding affinity toward HR1 compared to a control peptide EK1 (a modified pan-coronavirus fusion inhibitor) in molecular docking. To explore the time-dependent interactions of the fusion peptide with HR1, molecular dynamics simulation was performed incorporating lipid membrane. During 100 ns MD simulation, structural and energy parameters of Fp13-HR1 and Fp14-HR1 complexes demonstrated lower fluctuations compared to the control EK1-HR1 complex. Furthermore, principal component analysis and free energy landscape study revealed that these two peptides (Fp13 and Fp14) strongly bind to the HR1 with higher affinity than that of control EK1. Tyr917, Asn919, Gln926, lys933, and Gln949 residues in HR1 protein were found to be crucial residues for peptide interaction. Notably, Fp13, Fp14 showed reasonably better binding free energy and hydrogen bond contribution than that of EK1. Taken together, Fp13 and Fp14 peptides may be highly specific for HR1 which can potentially prevent the formation of the fusion core and could be further developed as therapeutics for treatment or prophylaxis of SARS-CoV-2 infection.
    MeSH term(s) Antiviral Agents/chemistry ; Antiviral Agents/pharmacology ; Humans ; Microbial Sensitivity Tests ; Peptides/chemistry ; Peptides/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/antagonists & inhibitors ; Spike Glycoprotein, Coronavirus/metabolism
    Chemical Substances Antiviral Agents ; Peptides ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-09-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1479181-X
    ISSN 1096-987X ; 0192-8651
    ISSN (online) 1096-987X
    ISSN 0192-8651
    DOI 10.1002/jcc.26758
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Designing potent inhibitors against the multidrug resistance P-glycoprotein.

    Mahmud, Shafi / Islam, Md Jahirul / Parves, Md Rimon / Khan, Md Arif / Tabussum, Lamiya / Ahmed, Sinthyia / Ali, Md Ackas / Fakayode, Sayo O / Halim, Mohammad A

    Journal of biomolecular structure & dynamics

    2021  Volume 40, Issue 19, Page(s) 9403–9415

    Abstract: The multidrug transporter P-glycoprotein is an ATP binding cassette (ABC) exporter responsible for resistance to tumor cells during chemotherapy. This study was designed with computational approaches aimed at identifying the best potent inhibitors of P- ... ...

    Abstract The multidrug transporter P-glycoprotein is an ATP binding cassette (ABC) exporter responsible for resistance to tumor cells during chemotherapy. This study was designed with computational approaches aimed at identifying the best potent inhibitors of P-glycoprotein. Although many compounds have been suggested to inhibit P-glycoprotein, however, their information on bioavailability, selectivity, ADMET properties, and molecular interactions has not been revealed. Molecular docking, ADMET analysis, molecular dynamics, Principal component analysis (PCA), and binding free energy calculations were performed. Two compounds D1 and D2 showed the best docking score against P-glycoprotein and both compounds have 4-thiazolidinone derivatives containing indolin-3 one moiety are novel anti-tumor compounds. ADMET calculation analysis predicted D1 and D2 to have acceptable pharmacokinetic properties. The MD simulation discloses that D1-P-glycoprotein and D2-P-glycoprotein complexes are in stable conformation as apo-form. Hydrophobic amino acid such as phenylalanine plays significant on the interactions of inhibitors. Principal component analysis shows that both complexes are relatively similar variables as apo-form except planarity and Columbo energy profile. In addition, Quantitative Structural Activity Relationship (QSAR) of the ligand candidates were subjected to the principal component analysis (PCA) for pattern recognition. Partial-least-square (PLS) regression analysis was further utilized to model drug candidates' QSAR for subsequent prediction of the binding energy of validated drug candidates. PCA revealed groupings of the drug candidates based on the similarity or differences in drug candidates QSAR. Moreover, the developed PLS regression accurately predicted the values of the binding energy of drug candidates, with low residual error of prediction.Communicated by Ramaswamy H. Sarma.
    Language English
    Publishing date 2021-06-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2021.1930159
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Investigating the binding affinity, interaction, and structure-activity-relationship of 76 prescription antiviral drugs targeting RdRp and Mpro of SARS-CoV-2.

    Ahmed, Sinthyia / Mahtarin, Rumana / Ahmed, Sayeda Samina / Akter, Shaila / Islam, Md Shamiul / Mamun, Abdulla Al / Islam, Rajib / Hossain, Md Nayeem / Ali, Md Ackas / Sultana, Mossammad U C / Parves, Md Rimon / Ullah, M Obayed / Halim, Mohammad A

    Journal of biomolecular structure & dynamics

    2020  Volume 39, Issue 16, Page(s) 6290–6305

    Abstract: SARS-CoV-2 virus outbreak poses a major threat to humans worldwide due to its highly contagious nature. In this study, molecular docking, molecular dynamics, and structure-activity relationship are employed to assess the binding affinity and interaction ... ...

    Abstract SARS-CoV-2 virus outbreak poses a major threat to humans worldwide due to its highly contagious nature. In this study, molecular docking, molecular dynamics, and structure-activity relationship are employed to assess the binding affinity and interaction of 76 prescription drugs against RNA dependent RNA polymerase (RdRp) and Main Protease (Mpro) of SARS-CoV-2. The RNA-dependent RNA polymerase is a vital enzyme of coronavirus replication/transcription complex whereas the main protease acts on the proteolysis of replicase polyproteins. Among 76 prescription antiviral drugs, four drugs (Raltegravir, Simeprevir, Cobicistat, and Daclatasvir) that are previously used for human immunodeficiency virus (HIV), hepatitis C virus (HCV), Ebola, and Marburg virus show higher binding energy and strong interaction with active sites of the receptor proteins. To explore the dynamic nature of the interaction, 100 ns molecular dynamics (MD) simulation is performed on the selected protein-drug complexes and apo-protein. Binding free energy of the selected drugs is performed by MM/PBSA. Besides docking and dynamics, partial least square (PLS) regression method is applied for the quantitative structure activity relationship to generate and predict the binding energy for drugs. PLS regression satisfactorily predicts the binding energy of the effective antiviral drugs compared to binding energy achieved from molecular docking with a precision of 85%. This study highly recommends researchers to screen these potential drugs in vitro and in vivo against SARS-CoV-2 for further validation of utility.
    MeSH term(s) Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; COVID-19 ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Peptide Hydrolases ; Prescription Drugs ; Prescriptions ; RNA-Dependent RNA Polymerase ; SARS-CoV-2 ; Structure-Activity Relationship
    Chemical Substances Antiviral Agents ; Prescription Drugs ; RNA-Dependent RNA Polymerase (EC 2.7.7.48) ; Peptide Hydrolases (EC 3.4.-)
    Keywords covid19
    Language English
    Publishing date 2020-07-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2020.1796804
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Cysteine focused covalent inhibitors against the main protease of SARS-CoV-2.

    Paul, Archi Sundar / Islam, Rajib / Parves, Md Rimon / Mamun, Abdulla Al / Shahriar, Imrul / Hossain, Md Imran / Hossain, Md Nayeem / Ali, Md Ackas / Halim, Mohammad A

    Journal of biomolecular structure & dynamics

    2020  Volume 40, Issue 4, Page(s) 1639–1658

    Abstract: In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys-His catalytic dyad, and ligands that interact with the Cys145 assumed to be ... ...

    Abstract In viral replication and transcription, the main protease (Mpro) of SARS-CoV-2 plays an important role and appears to be a vital target for drug design. In Mpro, there is a Cys-His catalytic dyad, and ligands that interact with the Cys145 assumed to be an effective approach to inhibit the Mpro. In this study, approximately 1400 cysteine-focused ligands were screened to identify the best candidates that can act as potent inhibitors against Mpro. Our results show that the selected ligands strongly interact with the key Cys145 and His41 residues. Covalent docking was performed for the selected candidates containing the acrylonitrile group, which can form a covalent bond with Cys145. All atoms molecular dynamics (MD) simulation was performed on the selected four inhibitors including L1, L2, L3 and L4 to validate the docking interactions. Our results were also compared with a control ligand, α-ketoamide (11r). Principal component analysis on structural and energy data obtained from the MD trajectories shows that L1, L3, L4 and α-ketoamide (11r) have structural similarity with the apo-form of the Mpro. Quantitative structure-activity relationship method was employed for pattern recognition of the best ligands, which discloses that ligands containing acrylonitrile and amide warheads can show better performance. ADMET analysis displays that our selected candidates appear to be safer inhibitors. Our combined studies suggest that the best cysteine focused ligands can help to design an effective lead drug for COVID-19 treatment. Communicated by Ramaswamy H. Sarma.
    MeSH term(s) COVID-19 ; Coronavirus 3C Proteases/antagonists & inhibitors ; Cysteine ; Humans ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Protease Inhibitors/pharmacology ; SARS-CoV-2/drug effects ; SARS-CoV-2/enzymology ; Structure-Activity Relationship
    Chemical Substances Protease Inhibitors ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28) ; Cysteine (K848JZ4886)
    Keywords covid19
    Language English
    Publishing date 2020-10-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2020.1831610
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top