Molecular Dynamics Simulation Study of N-14 Side Chain Substituted Styelsamines Binding to DNA

Abstract

N-14 side chain substituted marine styelsamines are synthesized ligands that have been evaluated for DNA binding and antitumor activity. Experimental data show that these ligands bind to DNA, but its binding position on DNA structure is unclear. In the present study, binding position and binding affinity of substituted styelsamines to DNA structure were studied using docking method, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MMGBSA) analysis. Initial docked complexes were created by inserting an intercalation site between DNA base pairs. MD simulations on all complexes were carried out for 15 ns. MMGBSA analysis was used for determination of the binding energy and entropy. Comparison of the predicted binding energies to experimental IC 50 values shows that the predicted binding energies increase with decreasing experimental IC 50 values. So, it was concluded that the initial docked structures are reliable. Moreover, MMGBSA analysis showed that van der Waals energy term is the major term in predicted binding energy.