Binding of a diverse set of ligands to avidin and streptavidin: An accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models
Binding of a diverse set of ligands to avidin and streptavidin: An accurate quantitative prediction of their relative affinities by a combination of molecular mechanics and continuum solvent models
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DOI：
10.1021/jm000241h
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发表时间：
2000-10-05
影响因子：
7.3
通讯作者：
Kollman, PA
中科院分区：
文献类型：
--
作者：
Kuhn, B;Kollman, PA
我们报告计算的自由能的结合，Δ G（结合），一组不同的9个配体和亲和素之间，以及之间的肽和链霉亲和素使用最近开发的MM/PBSA方法。该方法利用配体-蛋白质复合物的分子动力学模拟来产生参与复合物形成的分子的构象的热平均系综。基于这组结构，使用分子机械能和连续溶剂能以及非极性溶剂化自由能和溶质熵的估计来计算结合自由能。我们在模拟中比较了不同种类的配体，包括生物素衍生物、染料2-（4 '-羟基偶氮苯）苯甲酸（HABA）和环状六肽，它们涵盖了从-5到-20 kcal/mol的大范围的结合自由能。我们的计算能够再现实验Δ G（结合）值，具有非常好的相关系数r（2）= 0.92。这种一致性比用另一种方法，线性相互作用能近似，对于这个系统（r（2）= 0.55）得到的结果要好得多。
We report calculations of free energies of binding, Delta G(bind), between a diverse set of nine ligands and avidin as well as between a peptide and streptavidin using the recently developed MM/PBSA approach. This method makes use of a molecular dynamics simulation of the ligand-protein complex to generate a thermally averaged ensemble of conformations of the molecules that are involved in the complex formation. Based on this set of structures, a free energy of binding is calculated using molecular mechanical and continuum solvent energies as well as including estimates of the nonpolar solvation free energy and solute entropy. We compare in our simulations different classes of ligands, involving biotin derivatives, the dye 2-(4'-hydroxyazobenzene)benzoic acid (HABA), and a cyclic hexapeptide, which cover a large range of binding free energies from -5 to -20 kcal/mol. Our calculations are able to reproduce experimental Delta G(bind) values with a very good correlation coefficient of r(2) = 0.92. This agreement is considerably better than the results obtained with an alternate approach, the linear interaction energy approximation, for this system (r(2) = 0.55).