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
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 frontier orbitals of molecules of the eight probable target compounds (I, V-XI) were examined utilizing the computational approach wb97xd/6-311++g(d,p).
The frontier orbitals of molecules of the eight probable target compounds (I, V-XI) were examined utilizing the computational approach wb97xd/6-311++g(d,p).</p
The binding energy score and biological activity of the eight compounds.
The binding energy score and biological activity of the eight compounds.</p
Values of the Condensed local electrophilicity (ElP)/nucleophilicity (NuP) index (e*eV) of selected potential target compounds (V-IX) 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 (V-IX) by using wb97xd/6-311++g(d,p) level of theory from CDFT point of view.</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
The RMSD analysis for the entire residues of the eight compounds in complex with their target.
The RMSD analysis for the entire residues of the eight compounds in complex with their target.</p
MEP surfaces of selected potential eight target compounds (I, V-XI) utilizing the level of computation wb97xd/6-311++g(d,p).
MEP surfaces of selected potential eight target compounds (I, V-XI) utilizing the level of computation wb97xd/6-311++g(d,p).</p
The selected bond length (Å), bond angles and dihedral angles, (degree) of selected potential target compounds Deltarazin and Deltaflexin derivatives (I, X- XI) using wb97xd/6-311++g(d,p) level of theory; S4 Table: 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.
The selected bond length (Å), bond angles and dihedral angles, (degree) of selected potential target compounds Deltarazin and Deltaflexin derivatives (I, X- XI) using wb97xd/6-311++g(d,p) level of theory; S4 Table: 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 Fukui functions and Dual descriptor of selected potential target compounds (I, X-XI) using wb97xd/6-311++g(d,p) level of theory.
Values of the Fukui functions and Dual descriptor of selected potential target compounds (I, X-XI) using wb97xd/6-311++g(d,p) level of theory.</p