Molecular dynamics simulation of the interaction between human CD38 and some quinoline derivative inhibitors using reactive force field

Abstract

The paper presented initial calculated results obtained by molecular dynamics simulations of some CD38- micro and nanomolar inhibitor systems in vacuum using reactive force field ReaxFF. The ReaxFF software integrated in SCM's ADF has been used. The analysis and processing of results has been supplemented by VMD, CHIMERA and some external support softwares. The initial results showed that there are some associations between the inhibitor activity and the parameters compared apo and complex conlìgurations. In particular, the higher the activity, the greater the difference in protein backbone RMSD between apo and complex. Nanomolar inhibitor molecules approached closer to the AC1 active site residues, especially GLU¹⁴⁶ than micromolar one. In addition, the averaged and maximum fluctuation value of residues is also proportional to inhibitory activity. These can be considered suggestions for continuing to clarify the mechanism of CD38 inhibition of different ligand types supporting to the prediction and recommendation of new high active inhibitors.