Network metrics, structural dynamics and density functional theory calculations identified a novel Ursodeoxycholic Acid derivative against therapeutic target Parkin for Parkinson's disease

Mechanistic insights into the role of vitamin D and computational identification of potential lead compounds for Parkinson's disease

“…29 HOMO and LUMO frontier molecular orbitals calculated from DFT structure optimization simulations provided functional insights into leads' chemical stability and reactivity. 30 The identified three hits are more chemically reactive in the range of −0.20455 to −0.02457 eV, indicating a high intensity of polarization due to significant changes in the docking scores. The MESP, HOMO, and LUMO results were indicated that the identfied hits act as electron transfer ability (donor/acceptor) and which is more correlated with molecular docking protein-ligand interaction outcomes.…”

“…According to Jie Dong et al, 29 NURR1‐activating compounds can be developed based on the binding of LBD to helices 11 and 12 29 . HOMO and LUMO frontier molecular orbitals calculated from DFT structure optimization simulations provided functional insights into leads’ chemical stability and reactivity 30 . The identified three hits are more chemically reactive in the range of −0.20455 to −0.02457 eV, indicating a high intensity of polarization due to significant changes in the docking scores.…”

Translational protein RpsE as an alternative target for novel nucleoside analogues to treat MDR Enterobacter cloacae ATCC 13047: network analysis and molecular dynamics study

“…The top-ranked hub gene attaining the highest clustering and topological coefficients, along with functional relevance in the network was selected and the structure of its encoded protein was predicted. In case the structure was unavailable in the Protein Data Bank (PDB) ( https://www.rcsb.org/ ), the 3D structure of the protein was modeled as per the ‘extended dual-step modeling method’ as proposed by Basu et al ( 2021 ) to minimize the local conformational errors thus enhancing the gross accuracy of the model (Shankar et al 2021 ; Basu et al 2021 ; Naha et al 2022 ). The generation of the 3D model was based on homology (template-based) modeling and threading with I-TASSER ( https://zhanglab.ccmb.med.umich.edu/I-TASSER/ ), RaptorX ( http://raptorx.uchicago.edu/ ), and Robetta ( https://robetta.bakerlab.org/ ) servers (Kim et al 2004 ; Yang and Zhang 2015 ; Wang et al 2016 ).…”

“…Long-range electrostatic interactions were treated using particle-mesh Ewald algorithm with a cubic interpolation of order 4.0 and Fourier spacing of 0.16 nm (Jayaraman et al 2021 ). Finally, the system was subjected to MD production for 100,000ps timescale (Lemkul 2019 ; Miryala et al 2021b ; Naha et al 2022 ).…”

“…Computational studies have already been established to predict potential techniques and therapeutics in the field of medical research and diagnostic purposes (Sinha et al 2019 ; Godara and Kao 2020 ; Sharma et al 2021 ; Priyamvada et al 2022 ; Kaviraj et al 2022 ; Alam et al 2023 ; Choudhary et al 2023 ). Gene Interaction Network (GIN) approach integrated with structural bioinformatics can be useful in understanding the complex molecular interactions among the biomolecules present in the physiological systems (Naha et al 2022 ; Priyamvada et al 2022 ; Ashok and Ramaiah 2022 ). Our research group has previously decoded complex metabolic pathways and identified potent drug targets using network biology studies (Ashok et al 2021 , 2022 ; Naha and Ramaiah 2022 ), as well as integrated structural bioinformatics to predict effective lead molecules to circumvent several infectious and systemic diseases (Vasudevan et al 2021 ; Miryala et al 2021b ; Debroy and Ramaiah 2022 ).…”