Free-energy calculations of protein-ligand cation-π and amino-π interactions: From vacuum to proteinlike environments
Free-energy calculations of protein-ligand cation-π and amino-π interactions: From vacuum to proteinlike environments
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DOI：
10.1021/ja035223e
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发表时间：
2003-11-19
影响因子：
15
通讯作者：
Rooman, M
中科院分区：
文献类型：
--
作者：
Biot, C;Buisine, E;Rooman, M
为了探测阳离子-π和氨基-π相互作用在蛋白质-配体相互作用的背景下的作用，使用量子化学计算评估了涉及辅因子分子的Ade部分和其宿主蛋白的Arg、Lys、Asn或Gln侧链的55个X射线阳离子/氨基-π基序的稳定性。真空相互作用能、振动熵和溶剂化贡献的结合导致将Arg-Ade鉴定为所考虑的溶剂中最有利的阳离子/氨基-pi复合物，其次是Asn/Gln-Ade和Lys-Ade：它们的最小相互作用自由能分别约等于-7、-4和-2 kcal/mol，在介电常数类似于蛋白质的介电常数的溶剂中（即，丙酮、THF和CCl 4）。值得注意的是，阳离子/氨基-π相互作用的这些自由能值与它们在蛋白质-配体结构中的出现频率密切相关，这在缺乏实验数据的情况下证实了我们的方法。
To probe the role of cation-pi and amino-pi interactions in the context of protein-ligand interactions, the stability of 55 X-ray cation/amino-pi motifs involving the Ade moieties of cofactor molecules and Arg, Lys, Asn, or Gin side chains of their host protein was evaluated using quantum chemistry calculations. The conjunction of vacuum interaction energies, vibrational entropy, and solvation contributions led to identify Arg-Ade as the most favorable cation/amino-pi complex in the solvents considered, followed by Asn/Gln-Ade and Lys-Ade: their minimum interaction free energies are approximately equal to -7, -4, and -2 kcal/mol, respectively, in the solvents of dielectric constant similar to that estimated for proteins (i.e., acetone, THF, and CCl4). Remarkably, these free-energy values of cation/amino-pi interactions correlate well with their frequency of occurrences in protein-ligand structures, which corroborates our approach in the absence of experimental data.