2018
DOI: 10.1039/c7cp07623a
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Assessing the performance of MM/PBSA and MM/GBSA methods. 7. Entropy effects on the performance of end-point binding free energy calculation approaches

Abstract: Entropy effects play an important role in drug-target interactions, but the entropic contribution to ligand-binding affinity is often neglected by end-point binding free energy calculation methods, such as MM/GBSA and MM/PBSA, due to the expensive computational cost of normal mode analysis (NMA). Here, we systematically investigated entropy effects on the prediction power of MM/GBSA and MM/PBSA using >1500 protein-ligand systems and six representative AMBER force fields. Two computationally efficient methods, … Show more

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Cited by 261 publications
(215 citation statements)
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“…On the other hand, the molecular mechanical force field (MMFF)-based scoring functions, are physical and more accurate, but much less efficient. With the ever increasing computer power, MMFF-based free energy calculation methods, such as the endpoint MM-PB/GBSA (molecular mechanics-Poisson Boltzmann/ Generalized Born Surface Area) methods 2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21] and the alchemical thermodynamic integration (TI) and free energy perturbation (FEP) methods, 22,23 have been extensively applied in structure-based drug discovery projects. Recently we've developed a hierarchical virtual screening (HVS)to balance the efficiency and accuracy and improve the success rate of rational drug design.…”
Section: Introductionmentioning
confidence: 99%
“…On the other hand, the molecular mechanical force field (MMFF)-based scoring functions, are physical and more accurate, but much less efficient. With the ever increasing computer power, MMFF-based free energy calculation methods, such as the endpoint MM-PB/GBSA (molecular mechanics-Poisson Boltzmann/ Generalized Born Surface Area) methods 2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21] and the alchemical thermodynamic integration (TI) and free energy perturbation (FEP) methods, 22,23 have been extensively applied in structure-based drug discovery projects. Recently we've developed a hierarchical virtual screening (HVS)to balance the efficiency and accuracy and improve the success rate of rational drug design.…”
Section: Introductionmentioning
confidence: 99%
“…A variety of techniques, including conventional MD, umbrella sampling (US), and MM/GBSA approaches, were employed to explore how L884P mutation affected the binding of BBT594 and CGZ868 to JAK2 (Kong et al., ). MD simulations and MM/GBSA calculations (Chen et al., , ; Du et al., ; Hou, Wang, Li, & Wang, ; Kong et al., ; Lyne, Lamb, & Saeh, ; Niu, Pan, Yang, Liu, & Yao, ; Sun, Li, Tian, Xu, & Hou, ; Sun et al., , ; Zoete, Meuwly, & Karplus, ) have been widely applied to investigate the structure–affinity relationship for many biology systems including kinases. For instance, they were utilized to identify the key residues of extracellular‐regulated protein kinase 2 (ERK2) in the binding of four potent inhibitors (Niu et al., ).…”
Section: Introductionmentioning
confidence: 99%
“…However, the Δ G pred value is comparable to its analogue Amox (Kong et al, ). The relative rigid molecule structures with fewer flexible bonds in N ‐Des and Amox introduce less entropy loss upon the binding, and the omission of entropy term may lead to the underestimation of binding free energy for this kind of molecules (Chen et al, ; Hou, Wang, Li, & Wang, ; Hou, Wang, Li, & Wang, ; Huang et al, ; Jiang et al, ; Lu, Shen, & Zhang, ; Sun et al, ; Sun, Li, Shen, et al, ; Sun, Li, Tian, Xu, & Hou, ; Wang et al, ; Xu, Sun, Li, Wang, & Hou, ). The non‐polar energy contributions (Δ E vdw + Δ G SA ) are the primary favorable terms in the binding free energy and determine the binding affinities of the studied compounds (Table ).…”
Section: Resultsmentioning
confidence: 99%