Assessment of Available AMBER Force Fields to Model DNA-Ligand Interactions

Abstract

Deoxyribonucleic acid, commonly referred to as DNA is a promising cellular target for anticancer agents. The interaction of drugs with nucleic acid is an essential feature of pharmacology. It has a pivotal role in understanding the mechanism of drug action and developing more efficient drugs with fewer side effects. Molecular Dynamics (MD) simulations are widely used to study the effects of ligand binding and stability with biomolecular systems. To obtain the best force field, we have assessed the performance of seven available versions of AMBER force fields available with the framework of GROMACS software suite. A minor groove binding ligand was put under 100ns MD simulation under all seven force fields. We performed a total of 700ns (0.7µs) of MD simulations for our assessment. The analysis of MD results revealed that among all the seven AMBER versions, AMBER99SB gives the best results, and the parameterization using AMBER94 was not proper. However, the DNA remains intact for all force fields for the whole duration of the simulation.