Computational protocol: PMS1077 Sensitizes TNF-α Induced Apoptosis in Human Prostate Cancer Cells by Blocking NF-κB Signaling Pathway

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Protocol publication

[…] The IKK-β kinase domain (residues 16–310) was extracted from crystal structure of IKK-β in complex with an inhibitor (PDB ID: 3RZF) . Compounds PMS1077 and PMS601 were built using Avogadro, with MMFF94 force field energy minimization including 5000 steps of steepest descent and 2000 steps of conjugate gradients . All the structures for docking were prepared using AutoDockTools . Gasteiger charge and merging non-polar hydrogens were added.Molecular docking was performed by Autodock Vina . Compounds were set as flexible structures, and the binding conformers were searched using Iterated Local Search global optimizer. Final binding conformers were chosen according to the best AutoDock Vina score, combining of knowledge-based and empirical approach .(1)Here, ΔG is total binding energy; ΔGgauss is two gaussian functions containing attractive term of dispersion; ΔGrepulsion is the square of d (surface distance) when d<0; ΔGhydrophobic and ΔGhbond are hydrophobic interactions and hydrogen bonds, respectively; and ΔGtors is compound rotatable bonds.The binding affinity was also evaluated using AutoDock sore 4.1 () and NNScore 2.0 .(2)Here, Wvdw, Whbond, Welec, and Wsol are the weighting constants of Van der Waals interactions, hydrogen bonds, electrostatic interactions, and desolvation energy, respectively; Wtor is the weight of compounds torsion.NNScore 2.2 takes much more receptor-ligand characteristics to contribute for binding affinity, including AutoDock Vina's terms and 12 distinct binding characteristics from BINANA . In the present study, BINANA and Ligplot+ were introduced to analyze interaction of PMS1077 and IKK-β. […]

Pipeline specifications

Software tools Avogadro, AutoDock, AutoDock Vina, BINANA, LigPlot+
Applications Drug design, Protein interaction analysis
Organisms Homo sapiens
Diseases Neoplasms, Prostatic Neoplasms