Molecular Dynamics Investigation on a Series of HIV Protease Inhibitors: Assessing the Performance of MM-PBSA and MM-GBSA Approaches

Citations Over TimeTop 10% of 2012 papers

Abstract

The binding free energies (ΔG(Bind)) obtained from molecular mechanics with Poisson-Boltzmann surface area (MM-PBSA) or molecular mechanics with Generalized Born surface area (MM-GBSA) calculations using molecular dynamics (MD) trajectories are the most popular procedures to measure the strength of interactions between a ligand and its receptor. Several attempts have been made to correlate the ΔG(Bind) and experimental IC(50) values in order to observe the relationship between binding strength of a ligand (with its receptor) and its inhibitory activity. The duration of MD simulations seems very important for getting acceptable correlation. Here, we are presenting a systematic study to estimate the reasonable MD simulation time for acceptable correlation between ΔG(Bind) and experimental IC(50) values. A comparison between MM-PBSA and MM-GBSA approaches is also presented at various time scales. MD simulations (10 ns) for 14 HIV protease inhibitors have been carried out by using the Amber program. MM-PBSA/GBSA based ΔG(Bind) have been calculated and correlated with experimental IC(50) values at different time scales (0-1 to 0-10 ns). This study clearly demonstrates that the MM-PBSA based ΔG(Bind) (ΔG(Bind)-PB) values provide very good correlation with experimental IC(50) values (quantitative and qualitative) when MD simulation is carried out for a longer time; however, MM-GBSA based ΔG(Bind) (ΔG(Bind)-GB) values show acceptable correlation for shorter time of simulation also. The accuracy of ΔG(Bind)-PB increases and ΔG(Bind)-GB remains almost constant with the increasing time of simulation.

Related Papers

• → Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation(2014)78 cited
• → Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations(2012)34 cited
• → Combined Electrostatically Embedded Multiconfiguration Molecular Mechanics and Molecular Mechanical Method: Application to Molecular Dynamics Simulation of a Chemical Reaction in Aqueous Solution with Hybrid Density Functional Theory(2008)33 cited
• → Conformation and dynamics of a cyclic (1 → 2)-β-d-glucan(1995)30 cited
• → MOLECULAR DYNAMICS SIMULATIONS OF THE STK630921 INTERACTIONS TO INTERLEUKIN-17A(2023)3 cited