Efficient estimation of MMGBSA-based BEs for DNA and aromatic furan amidino derivatives

Abstract

Molecular mechanics with Generalized Born surface area (MMGBSA) based binding energies (BEs) derived from the molecular dynamics (MD) trajectories are highly reliable and extensively used standards to estimate the strength of interactions between ligands and their receptor. MD simulations (5 ns) for 30 aromatic furan aminidino derivatives (anti-Pneumocystis carnii agents) have been carried out by using Amber program and BEs have been calculated by using Generalized Born (GB) method. Based on the generated data, we present a simple and effective method for the approximation of BEs without performing MD simulations and MMGBSA calculations. Quantum chemical (density functional theory based) and geometrical descriptors are used for the prediction of the BE values. All the developed models are statistically significant with high values of correlation and cross-validation coefficients. The prediction ability and effectiveness of the models are tested by the division of the data-set into four different training and test sets and the average error was only 4–7% (1.56–2.61 kcal/mol) of the actual BEs.

Keywords:

• DNA minor groove binders
• MMGBSA-based BEs
• molecular dynamics simulations
• thermal stability of DNA–ligand complexes (ΔT _m values)
• Pneumocystis carnii agents
• DFT-based QSAR studies

Acknowledgments

HKS and GNS thank the Department of Science and Technology (DST), New Delhi for the financial assistance through Fast-Track (SR/FT/CS-031/2009) and Swarnajayanti projects respectively.