Elucidating the Energetics of Entropically Driven Protein-Ligand   Association: Calculations of Absolute Binding Free Energy and Entropy

doi:10.1021/jp204047b

CORC > 北京大学 > 化学与分子工程学院

	Elucidating the Energetics of Entropically Driven Protein-Ligand Association: Calculations of Absolute Binding Free Energy and Entropy
	Deng, Nan-jie ; Zhang, Peng ; Cieplak, Piotr ; Lai, Luhua
刊名	journal of physical chemistry b
	2011
关键词	HUMAN-IMMUNODEFICIENCY-VIRUS MOLECULAR-DYNAMICS SIMULATIONS HIV-1 PROTEASE DRUG DESIGN COMPUTER-SIMULATIONS ACCURATE PREDICTION STRUCTURAL BIOLOGY EXPLICIT SOLVENT WATER-MOLECULES INHIBITORS
DOI	10.1021/jp204047b
英文摘要	The binding of proteins and ligands is generally associated with the loss of translational, rotational, and conformational entropy. In many cases, however, the net entropy change due to binding is positive. To develop a deeper understanding of the energetics of entropically driven protein-ligand binding, we calculated the absolute binding free energies and binding entropies for two HIV-1 protease inhibitors Nelfinavir and Amprenavir using the double-decoupling method with molecular dynamics simulations in explicit solvent. For both ligands, the calculated absolute binding free energies are in general agreement with experiments. The statistical error in the computed Delta G(bind) due to convergence problem is estimated to be >= 2 kcal/mol. The decomposition of free energies indicates that, although the binding of Nelfinavir is driven by nonpolar interaction, Amprenavir binding benefits from both nonpolar and electrostatic interactions. The calculated absolute binding entropies show that (1) Nelfinavir binding is driven by large entropy change and (2) the entropy of Amprenavir binding is much less favorable compared with that of Nelfinavir. Both results are consistent with experiments. To obtain qualitative insights into the entropic effects, we decomposed the absolute binding entropy into different contributions based on the temperature dependence of free energies along different legs of the thermodynamic pathway. The results suggest that the favorable entropic contribution to binding is dominated by the ligand desolvation entropy. The entropy gain due to solvent release from binding site appears to be more than offset by the reduction of rotational and vibrational entropies upon binding.; Chemistry, Physical; SCI(E); EI; 11; ARTICLE; 41; 11902-11910; 115
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/237600]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Deng, Nan-jie,Zhang, Peng,Cieplak, Piotr,et al. Elucidating the Energetics of Entropically Driven Protein-Ligand Association: Calculations of Absolute Binding Free Energy and Entropy[J]. journal of physical chemistry b,2011.
APA	Deng, Nan-jie,Zhang, Peng,Cieplak, Piotr,&Lai, Luhua.(2011).Elucidating the Energetics of Entropically Driven Protein-Ligand Association: Calculations of Absolute Binding Free Energy and Entropy.journal of physical chemistry b.
MLA	Deng, Nan-jie,et al."Elucidating the Energetics of Entropically Driven Protein-Ligand Association: Calculations of Absolute Binding Free Energy and Entropy".journal of physical chemistry b (2011).