Akademik Veri Yönetim Sistemi
9 TH INTERNATIONAL BAU DRUG DESIGN CONGRESS, İstanbul, Türkiye, 29 Kasım - 02 Aralık 2023, ss.109
Spleen Tyrosine Kinase (SYK) which is a non-receptor kinase crosstalk pivotal signaling
pathways such as PI3K, NFκB and JAK/STAT that play a role in pathogenesis of various
cancers. Syk is composed of two SH2 domains at the amino terminus, followed by a
catalytically active kinase domain. In this study, we aim to target the C-SH2 domain of Syk
to prevent cancer progression. We employed a virtual screening of a mid-scale chemical
library provided by COCONUT with 407,270 unique natural products. The chemical files of
the library were converted into 3D structure files using RDKIT as preparation step for
molecular docking via Smina. The target protein was selected as the crystal structure of the
protein complex (PDB entry: 18A1). The existing heteroatoms and the conjugated peptide
molecule were cleared, then the target binding region located on C-SH2 domain was
determined using Fpocket utility to prepare the protein molecule for docking. The docking
experiments yielded 25 ligand poses with a docking score less than -7.5. Three lead
candidates were selected and further tested with Molecular Dynamics simulations via
Gromacs for a duration of 100 ns. Post analysis of trajectories of three complexes revealed
one of the hit molecules is a more promising lead candidate, which is called Preussomerin B.
The multidrug resistance and poor prognosis reveal the requirement of more effective
treatments for cancer. Here, we suggested a novel strategy to target Syk by in silico
studies.