Theoretical study on the HIV-1 integrase-5CITEP complex based on polarized force fields

Molecular dynamics studies of 5CITEP binding with HIV-1 integrase (IN) are presented using both polarized and nonpolarized force fields. When nonpolarized force field is used, the ligand drifts away from the original binding site. However, this depressing behavior can be curbed by introducing electronic polarization effect into the force field that stabilizes the protein structure and keeps the ligand in the binding pocket. Moreover, simulation under polarized force field gives a binding energy of -4.85 kcal/mol which is in excellent agreement with the experimental ΔG of -4.38 kcal/mol. The results demonstrate the importance of intra-protein electronic polarization in stabilizing the binding complex of IN-5CITEP and accurately predicting the binding energy.