Combined pharmacophore, virtual screening and molecular dynamics studies to identify Bruton’s tyrosine kinase inhibitors

Abstract

Bruton's tyrosine Kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase expressed in hematopoietic cells. BTK plays a critical role in many cellular signalling pathways making it a potential target to treat autoimmune diseases and cancer. BTK signalling is important for the production of arthritis-associated antibodies, and inhibiting BTK will help the system to block the production of disease-associated antibodies. In this study, we have implemented ligand-based pharmacophore modelling and virtual screening against natural compounds followed by molecular docking, density functional theory and molecular dynamics studies for 50 ns. Four compounds with high affinity towards BTK were identified, and it could be used as a potent lead molecule for designing BTK inhibitor.

Identification of potential drugs targeting L,L‐diaminopimelate aminotransferase of Chlamydia trachomatis: An integrative pharmacoinformatics approach

“…The highest energy gap was observed in MFCD01312897 with the HOMO‐LUMO gap energy of ‐0.02517 eV and lowest gap energy was observed in NCI_41500 with the HOMO‐LUMO gap energy of ‐0.11703 eV. The best hits showed minimal HOMO‐LUMO gap with the average energy difference of ‐0.07 eV, signifying the chemical reactivity of these compounds …”

“…The best hits showed minimal HOMO-LUMO gap with the average energy difference of -0.07 eV, signifying the chemical reactivity of these compounds. 67,68 4.6 | Post-docking analysis of best "hits"…”

In-silico study of seaweed secondary metabolites as AXL kinase inhibitors

“…The selected five complexes protein–ligand were subjected to 100 ns (nanoseconds) simulations of molecular dynamics (MD) under constant pressure and temperature conditions and the stability of the molecules can be understood with simulations of MD complexes ( Sakthivel and Habeeb, 2018 , Tanneeru et al, 2015 , Tanneeru and Guruprasad, 2013 , Wan et al, 2019 ). All the simulations of MD were conducted by using Gromacs 2018, Ubuntu-18.04 LTS Linux platform.…”

Synthesis and theoretical analysis of interaction from an adamantane-steroid derivative with both COX-1 and COX-2

“…Several reports have shown that the pharmacophore model can be very useful to design new molecules with pharmacological activity. [34]. In this investigation, LigandScout software [14] was used to develop two pharmacophores from both compounds 3 and 4.…”