Inter Molecular Level Interaction Studies of Combination Drug Crizotinib And Temozolomide in Glioblastoma Multiforme Targets: An In-silico Approach

Combination drug treatments are frequently used in many diseases, including cancers and AIDS. The main aims of these treatments are to reduce toxicity, decrease or delay drug resistance, and improve drug efficacy by inhibiting the activity of a specific target or groups of targets in a cell. The net effect of combination drug efficacy is mainly quantified and interpreted by various terminologies like synergy, additive, agonism, and antagonism based on drugs dose ratio. In single or combination drug treatment, drug action occurs on cells due to the intermolecular level interaction of drugs with protein/DNA/RNA/Enzyme. This type of inter molecular level interaction can be detected with the help of docking software. The current study aims to identify the inter-molecular level interaction of combination drug Crizotinib and Temozolomide with C-MET, C-ROS1, and ALK targets in Glioblastoma Multiforme(GBM). To identify this, we performed forward and reverse docking of drugs with these proteins, and the results were evaluated by drug properties and the complex energy. From the analysis study, we recognized that first, Crizotinib and then, after Temozolomide bounded docked complexes showed the least complex energy in all the docked complex structures, and the better complexes were identified from the result by MD simulation.

Topological delocalization transitions and mobility edges in the nonreciprocal Maryland model

Non-Hermitian effects could trigger spectrum, localization and topological phase transitions in quasiperiodic lattices. We propose a non-Hermitian extension of the Maryland model, which forms a paradigm in the study of localization and quantum chaos by introducing asymmetry to its hopping amplitudes. The resulting nonreciprocal Maryland model is found to possess a real-to-complex spectrum transition at a finite amount of hopping asymmetry, through which it changes from a localized phase to a mobility edge phase. Explicit expressions of the complex energy dispersions, phase boundaries and mobility edges are found. A topological winding number is further introduced to characterize the transition between different phases. Our work introduces a unique type of non-Hermitian quasicrystal, which admits exactly obtainable phase diagrams, mobility edges, and holding no extended phases at finite nonreciprocity in the thermodynamic limit.

Docking and dynamic simulation study of Crizotinib and Temozolomide drug with Glioblastoma and NSCLC target to identify better efficacy of the drug

Background Crizotinib and Temozolomide are the two major chemotherapy drugs used for the treatment of cancers. Crizotinib is used as a target chemotherapy drug in many cancers. It mainly binds on the ATP binding regions of receptor tyrosine kinases (RTKs) targets and inhibits protein phosphorylation, which has already been reported. Temozolomide drug is known as the alkylating agent. Its mechanism of action is the methylation of DNA and thereby inhibiting DNA replication. However, the Temozolomide drug with protein level interaction of Glioblastoma Multiforme (GBM) and Non-small-cell lung carcinoma (NSCLC) of RTKs targets has not been reported so far. In the proposed work, we investigated the molecular level interaction of the Temozolomide drug in C-MET, C-ROS1, and ALK RTKs targets of GBM and NSCLC using an in silico study. We performed comparative analysis studies in both drugs' docked complexes based on their drug properties and complex energy (CE) to identify the better efficacy of the drug. Results From the docking studies, we could identify that the Temozolomide drug bounded protein complexes showed the least complex energy. The most stable complexes were identified from these docking studies by Molecular Dynamic simulation. In the proposed study, we found that the docked complex attained a stable conformation and least energy via solid hydrogen bond interactions between the amino acid residues and the drug at the binding sites of the proteins. The least energy and the hydrogen bond interaction of Temozolomide drug with the amino acid residues of the protein complexes of C-MET, C-ROS1 and ALK protein with their id name are: 2WGJ is − 11305.0830 (PRO1158, MET1160), 3ZBF is − 11,659.6814 (MET2029, GLU2027), and 2XP2 is − 11,734.7565 (ARG1275, ASP 1160, GLU1167). Conclusion Our studies revealed that the Temozolomide drug bounded protein complex showed the least energy when compared to Crizotinib. So it will give better interaction on the binding sites of proteins and thereby provide better inhibition in the treatment of target therapy of GBM and NSCLC.

Construction and Optimization of a Thermo-economic Cost Analysis Model for the Complex Energy Network

Improving the energy use efficiency of the energy system is of great significance to the development of the national energy economy and the improvement of the national economic competitiveness. The existing domestic research on thermo-economic costs is insufficient. For example, there is no research on the allocation of thermo-economic costs and on the complex energy network with multiple energy outputs. Therefore, this paper reconstructs and optimizes the thermo-economic cost analysis model for the complex energy network. First, the thermo-economic cost model for each sub-network and that for each energy output of the complex energy network were established, and the structure block diagram of the distributed thermo-economic cost allocation model for the complex energy network was given. Then, a local-global decomposition optimization method was proposed for the complex energy network to achieve the thermo-economic optimization of the complex energy network. The experimental results proved the effectiveness of the proposed algorithm.