human serum albumin (hsa) is the most abundant protein in the blood plasma. drug binding to hsa is crucial to study the absorption, distribution, metabolism, efficiency and bioavailability of drug molecules. in this study, isothermal titration calorimetry and molecular dynamics simulation of hsa and its complex with indometacin (im) were performed to investigate thermodynamics parameters and th...

The pH-driven opening and closure of beta-lactoglobulin EF loop, acting as a lid and closing the internal cavity of the protein, has been studied by molecular dynamics (MD) simulations and free energy calculations based on molecular mechanics/Poisson-Boltzmann (PB) solvent-accessible surface area (MM/PBSA) methodology. The forms above and below the transition pH differ presumably only in the pr...

Here, we systematically investigated how the force fields and the partial charge models for ligands affect the ranking performance of the binding free energies predicted by the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) approaches. A total of 46 small molecules targeted to five different protein receptors were emp...

In molecular docking, it is challenging to develop a scoring function that is accurate to conduct high-throughput screenings. Most scoring functions implemented in popular docking software packages were developed with many approximations for computational efficiency, which sacrifices the accuracy of prediction. With advanced technology and powerful computational hardware nowadays, it is feasibl...

The Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) and the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) methods calculate binding free energies for macromolecules by combining molecular mechanics calculations and continuum solvation models. To systematically evaluate the performance of these methods, we report here an extensive study of 59 ligands interacting with s...

Protein kinase CK2, also known as casein kinase II, is related to various cellular events and is a potential target for numerous cancers. In this study, we attempted to gain more insight into the inhibition process of CK2 by a series of CX-4945 derivatives through an integrated computational study that combines molecular docking, molecular dynamics (MD) simulations, and binding free energy calc...

By using different evaluation strategies, we systemically evaluated the performance of Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) methodologies based on more than 1800 protein-ligand crystal structures in the PDBbind database. The results can be summarized as follows: (1) for the one-protein-family/one-binding-lig...

Human serum albumin (HSA) is the most abundant protein in the blood plasma. Drug binding to HSA is crucial to study the absorption, distribution, metabolism, efficiency and bioavailability of drug molecules. In this study, isothermal titration calorimetry and molecular dynamics simulation of HSA and its complex with indometacin (IM) were performed to investigate thermodynamics parameters and th...

We apply a high-throughput formulation of the molecular mechanics with Poisson-Boltzmann surface area (htMM-PBSA) to estimate relative binding potencies on a set of 308 small-molecule ligands in complex with the proteins urokinase, PTP-1B, and Chk-1. We observe statistically significant correlation to experimentally measured potencies and report correlation coefficients for the three proteins i...

We have applied the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method (J. Srinivasan, T. E. Cheatham, P. Cieplak, P. A. Kollman, and D. A. Case, Journal of the American Chemical Society, 1998, Vol. 120, pp. 9401-9409) to study the interaction of an RNA aptamer with theophylline and its analogs. The MM-PBSA free energy analysis provides a reasonable absolute binding free energy...