分子亲脂-亲水性的量子化学描述(Ⅰ)——分子的亲脂和亲水表面

Quantum Chemical Description for Molecular Lipophilicity and Hydrophilicity(Ⅰ) ——Molecular Lipophilic and Hydrophilic Surface

给出基于分子结构的“启发式”亲脂 -亲水势 HMLP ( Heuristic molecular lipophilicity-hydrophilicitypotential)的理论分析和有说服力的算例 .用量子化学计算其分子表面的静电势 V( r)的分布 ,通过与周围原子表面静电势的比较 ,构造表达分子静电势的极性和大小的函数 L( r) .亲脂势 L( r)保留了静电势 V( r)描述分子静电作用的能力 ,并把应用范围扩展到疏水性的描述 .HMLP不使用原子的经验参数 ,但在 L( r)的构造中使用了经验的函数形式 .经参数化和指标化后 ,HMLP有望用于蛋白质结构与功能的研究和药物分子配体与生物大分子受体结合自由能的估算 .

In this research the structure-based method, heuristic molecular lipophilicity-hydrophilicity potential (HMLP), describing of molecular lipophilicity and hydrophilicity potential on molecular surfaces was introduced. The ESP (electrostatic potential) V(r) on molecular van der Waals surface is calculated, then molecular lipophilicity potential L(r) is constructed by comparing the polarity with the ESP on the surrounding atoms through a screening function. HMLP can be used to describe the molecular interactions with polar and non-polar solvent molecules taking the advantage of the polarity of HMLP. Therefore, HMLP is a unified lipophilicity and hydrophilicity potential, its positive values represent lipophilicity and negative values represent hydrophilicity. Several examples given in this paper show that HMLP gives a better descriptions for ligand-receptor interaction than other methods, such as atomic partial charges and empirical lipophilicity potential. After parameterization and indexing, hopefully, HMLP may be applied to the studies of function and structure of proteins and the genomic decoding of DNA and RNA.