Interaction of carboranes with biomolecules:: Formation of dihydrogen bonds
Interaction of carboranes with biomolecules:: Formation of dihydrogen bonds
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DOI：
10.1002/cphc.200500648
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发表时间：
2006-05-12
期刊：
影响因子：
2.9
通讯作者：
Hobza, Pavel
中科院分区：
文献类型：
--
作者：
Fanfrlik, Jindrich;Lepsik, Martin;Hobza, Pavel
采用分子动力学方法，采用UFF经验势，研究了真空中多面体corborone 1-corbacloso-dodecaborone（CB 11 H12）（-）与生物分子结构单元甘氨酸（GLY）、丝氨酸（SER）、苯丙氨酸（PHE）、谷氨酸（GLU）、赖氨酸（LYS）和精氨酸（ARG）的非共价相互作用.通过精确的从头计算量子化学程序对选定的结构进行了进一步研究。还考虑了与肽键（GLY-SER二肽）和核酸结构单元（鸟嘌呤）的相互作用。碳硼烷和小模型系统的RESP和NPA电荷进行了比较，并讨论了它们的用途。碳硼烷和生物分子之间的主要相互作用是形成非常规的质子-氢化物氢键（二氢键），其特征在于氢原子之间的短距离（接近1.8埃）和平均强度在4.2-5.8 kcal mol（-1）范围内。所研究的复合物的总稳定化能相当大，其中最大值（约15 kcal mol（-1））出现在ARG和GLY-SER二肽的碳硼烷复合物中。这些相互作用在影响相互作用强度的几何约束下是普遍存在的。碳硼烷与生物分子形成二氢键，优选与其下半球的氢原子（即与碳原子相对的笼的部分）形成二氢键。这两个几何因子可以用来解释卡波酮抑制HIV蛋白酶的特异性。
Noncovalent interactions of the polyhedral corborone 1-corbacloso-dodecaborone (CB11H12)(-) with building blocks of biomolecules, modelled by glycine (GLY), serine (SER), phenylalanine (PHE), glutamic acid (GLU), lysine (LYS) and arginine (ARG), were investigated in vacua by molecular dynamics simulations with the UFF empirical potential. Selected structures were further studied by accurate ob initio quantum chemical procedures. Interactions with a peptide bond (GLY-SER dipeptide) and a nucleic acid building block (guanine) were also considered. The RESP and NPA charges of carboranes and small model systems are compared and their use is discussed. The dominant interaction between carboranes and biomolecules is the formation of unconventional proton-hydride hydrogen bonds (dihydrogen bonds) characterized by a short distance between hydrogen atoms (as close as 1.8 angstrom) and on average strength in the range of 4.2-5.8 kcal mol(-1). The total stabilization energy of complexes investigated is rather large, and the largest value (approximate to 15 kcal mol(-1)) was found for the carborane complexes with ARG and the GLY-SER dipeptide. These interactions are ubiquitous under geometrical constraints influencing the strength of the interaction. The carborane forms dihydrogen bonds with biomolecules preferably with the hydrogen atoms of its lower hemisphere (i.e. the part of the cage opposite to the carbon atom). These two geometrical factors can be used to explain the specificity of inhibition of HIV protease by carborones.