28 research outputs found
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DFT and molecular simulation validation of the binding activity of PDEδ inhibitors for repression of oncogenic k-Ras.
The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling
Structure for some reported KRAS‒PDEδ inhibitors.
The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling.</div
Physico-chemical properties analysis and QSAR properties of selected potential eight target compounds (I, V-XI) towards PDEδ inhibitors for repression of oncogenic k-Ras.
Physico-chemical properties analysis and QSAR properties of selected potential eight target compounds (I, V-XI) towards PDEδ inhibitors for repression of oncogenic k-Ras.</p
Values of the Condensed local electrophilicity (ElP)/nucleophilicity (NuP) index (e*eV) of selected potential target compounds (I, X-XI) by using wb97xd/6-311++g(d,p) level of theory from CDFT point of view.
Values of the Condensed local electrophilicity (ElP)/nucleophilicity (NuP) index (e*eV) of selected potential target compounds (I, X-XI) by using wb97xd/6-311++g(d,p) level of theory from CDFT point of view.</p
Natural charge of selected atoms of selected potential eight target compounds (I,V-XI) by using wb97xd/6-311++g(d,p) level of theory.
Natural charge of selected atoms of selected potential eight target compounds (I,V-XI) by using wb97xd/6-311++g(d,p) level of theory.</p
Values of the Condensed local Softnesses (Hartree*e) of selected potential target compounds (I, X, XI) by using wb97xd/6-311++g(d,p) level of theory from CDFT point of view.
Values of the Condensed local Softnesses (Hartree*e) of selected potential target compounds (I, X, XI) by using wb97xd/6-311++g(d,p) level of theory from CDFT point of view.</p
The selected bond length (Å), bond angles and dihedral angles, (degree) of the selected potential target compounds (V-IX) of Coumarin derivatives using wb97xd/6-311++g(d,p) level of theory verses the X-ray crystal structure data (CCDC: 697425) of 3-((2-Oxo-2H-chromen-3-yl)carbonyl)pyridinium hydrogen squarate.
The selected bond length (Å), bond angles and dihedral angles, (degree) of the selected potential target compounds (V-IX) of Coumarin derivatives using wb97xd/6-311++g(d,p) level of theory verses the X-ray crystal structure data (CCDC: 697425) of 3-((2-Oxo-2H-chromen-3-yl)carbonyl)pyridinium hydrogen squarate.</p
The RG calculation through the entire MD.
The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling.</div
The RMSD of the eight complexes at their maximum fluctuation.
The RMSD of the eight complexes at their maximum fluctuation.</p
Molecular docking of the target compounds.
The development of effective drugs targeting the K-Ras oncogene product is a significant focus in anticancer drug development. Despite the lack of successful Ras signaling inhibitors, recent research has identified PDEδ, a KRAS transporter, as a potential target for inhibiting the oncogenic KRAS signaling pathway. This study aims to investigate the interactions between eight K-Ras inhibitors (deltarazine, deltaflexin 1 and 2, and its analogues) and PDEδ to understand their binding modes. The research will utilize computational techniques such as density functional theory (DFT) and molecular electrostatic surface potential (MESP), molecular docking, binding site analyses, molecular dynamic (MD) simulations, electronic structure computations, and predictions of the binding free energy. Molecular dynamic simulations (MD) will be used to predict the binding conformations and pharmacophoric features in the active site of PDEδ for the examined structures. The binding free energies determined using the MMPB(GB)SA method will be compared with the observed potency values of the tested compounds. This computational approach aims to enhance understanding of the PDEδ selective mechanism, which could contribute to the development of novel selective inhibitors for K-Ras signaling.</div