Protein-protein recognition and interaction hot spots in an antigen-antibody complex: Free energy decomposition identifies "efficient amino acids"
Protein-protein recognition and interaction hot spots in an antigen-antibody complex: Free energy decomposition identifies "efficient amino acids"
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DOI：
10.1002/prot.21259
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发表时间：
2007-05-01
影响因子：
2.9
通讯作者：
Dejaegere, Annick
中科院分区：
文献类型：
--
作者：
Lafont, Virginie;Schaefer, Michael;Dejaegere, Annick
应用分子力学Poisson-Boltzmann表面积（MAVPBSA）方法研究了骆驼单链可变区（cAb-Lys 3）与鸡蛋白色溶菌酶（BEL）、火鸡鸡蛋白色溶菌酶（TEL）之间的蛋白质-蛋白质复合物。通过求解线性Poisson-Boltzmann方程估计静电能。一个自由能分解计划，以确定结合能热点的每个复杂的。计算确定了抗体中对与溶菌酶的相互作用做出重要贡献的氨基酸。他们进一步展示了小的结构变化对结合能量学的影响，并且他们展示了构成热点的抗体氨基酸以模仿溶菌酶底物的方式组织。通过对结果的进一步分析，我们定义了“高效氨基酸”的概念，它可以提供对特定热点相互作用的结合潜力的评估。反过来，这些信息可以用于模拟抗体的小分子的合理设计。使用自由能分解，以确定区域的蛋白质-蛋白质复合物，可以通过小分子抑制剂的影响进行了讨论。
The molecular mechanics Poisson-Boltzmann surface area (MAVPBSA) method was applied to the study of the protein-protein complex between a camelid single chain variable domain (cAb-Lys3) and hen egg white lysozyme (BEL), and between cAb-Lys3 and turkey egg white lysozyme (TEL). The electrostatic energy was estimated by solving the linear Poisson-Boltzmann equation. A free energy decomposition scheme was developed to determine binding energy hot spots of each complex. The calculations identified amino acids of the antibody that make important contributions to the interaction with lysozyme. They further showed the influence of small structural variations on the energetics of binding and they showed that the antibody amino acids that make up the hot spots are organized in such a way as to mimic the lysozyme substrate. Through further analysis of the results, we define the concept of "efficient amino acids," which can provide an assessment of the binding potential of a particular hot spot interaction. This information, in turn, can be useful in the rational design of small molecules that mimic the antibody. The implications of using free energy decomposition to identify regions of a protein-protein complex that could be targeted by small molecules inhibitors are discussed.