Effect of sampling on BACE-1 ligands binding free energy predictions via MM-PBSA calculations
نویسندگان
چکیده
منابع مشابه
Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA
In the drug discovery process, accurate methods of computing the affinity of small molecules with a biological target are strongly needed. This is particularly true for molecular docking and virtual screening methods, which use approximated scoring functions and struggle in estimating binding energies in correlation with experimental values. Among the various methods, MM-PBSA and MM-GBSA are em...
متن کاملAssessing the Performance of the MM/PBSA and MM/GBSA Methods. 1. The Accuracy of Binding Free Energy Calculations Based on Molecular Dynamics Simulations
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...
متن کاملFree energy calculations for theophylline binding to an RNA aptamer: Comparison of MM-PBSA and thermodynamic integration methods.
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...
متن کاملExtension of the free energy workflow FEW towards implicit solvent/implicit membrane MM-PBSA calculations.
BACKGROUND The number of high-resolution structures of pharmacologically relevant membrane proteins has been strongly increasing. This makes computing relative affinities of chemically similar compounds binding to a membrane protein possible in order to guide decision making in drug design. However, the preparation step of such calculations is time-consuming and complex. METHODS We extended t...
متن کاملPredictions of Ligand Selectivity from Absolute Binding Free Energy Calculations
Binding selectivity is a requirement for the development of a safe drug, and it is a critical property for chemical probes used in preclinical target validation. Engineering selectivity adds considerable complexity to the rational design of new drugs, as it involves the optimization of multiple binding affinities. Computationally, the prediction of binding selectivity is a challenge, and genera...
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ژورنال
عنوان ژورنال: Journal of Computational Chemistry
سال: 2017
ISSN: 0192-8651
DOI: 10.1002/jcc.24839