Computer-aided identification of lead compounds as Staphylococcal epidermidis FtsZ inhibitors using molecular docking, virtual screening, DFT analysis, and molecular dynamic simulation

2019 ◽  
Vol 25 (12) ◽  
Author(s):  
Swayansiddha Tripathy ◽  
Susanta Kumar Sahu ◽  
Mohammed Afzal Azam ◽  
Srikanth Jupudi
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Molecular Dynamic Simulation ◽  
Molecular Dynamic ◽  
Dynamic Simulation ◽  
Lead Compounds ◽  
Computer Aided ◽  
Ftsz Inhibitors

scholarly journals AMPA GluA2 subunit competitive inhibitors for PICK1 PDZ domain: Pharmacophore-based virtual screening, molecular docking, molecular dynamic simulation, and ADME studies

2021 ◽  
Author(s):  
Shravan B. Rathod ◽  
Pravin B. Prajapati ◽  
Ranjan Pal
Keyword(s):  
Molecular Docking ◽  
Synaptic Plasticity ◽  
Virtual Screening ◽  
Molecular Dynamic Simulation ◽  
Molecular Dynamic ◽  
Dynamic Simulation ◽  
Neurological Diseases ◽  
Pdz Domain ◽  
Scaffolding Protein ◽  
Beneficial Effects

PICK1 (protein interacting with C kinase-1) plays a key role in the regulation of intracellular trafficking of AMPA GluA2 subunit that is linked with synaptic plasticity. PICK1 is a scaffolding protein and binds numerous proteins through its PDZ domain. Research showed that synaptic plasticity is altered upon disrupting the GluA2-PDZ interactions. Inhibiting PDZ and GluA2 binding lead to beneficial effects in the cure of neurological diseases thus, preventing PDZ-GluA2 binding is thought to novel therapeutic target in such diseases. To target this, generally, peptides were synthesized and tested. Though small organic molecules have been targeted to prevent these interactions, the number of such molecules is inadequate. Thus, in this study, ten molecular libraries containing large numbers of molecules were screened against the PDZ domain using pharmacophore-based virtual screening to find the best hits for the PDZ domain. Molecular docking, molecular dynamic simulation, and ADME analyses revealed that Hit_III (MolPort-005-050-255) shows efficient binding and drug likeness for the PDZ domain. This study suggests that tested hit may have potency against the PDZ domain and can be considered effective to treat neurological disorders.

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