Geller M, Shugar D
Drugs Exp Clin Res. 1986;12(6-7):595-612.
An attempt is made to delineate the scope and limitations, and future perspectives, of the theoretical methods being applied increasingly to various aspects of drug design and associated problems. The two methods of approach, quantum mechanics and statistical physics (Monte Carlo, Molecular Dynamics), are used to evaluate such properties as electron density distribution, structure and conformation, intermolecular interactions, etc. for isolated molecules and their autoassociates, and for interactions with the environment (e.g., solvent, receptor molecules). The validity of such calculations, dependent on factors such as geometrical optimalization, correlation energy and differing approximations of the form of the wave function, is illustrated in the case of enol-keto tautomerism of nitrogen heterocycles, relevant to the biological (including chemotherapeutic) activities of some nucleoside analogues. Intermolecular interactions, including the role of solvent, are assessed for purine and pyrimidines. The scope of the Molecular Dynamics methods is exemplified by its application to the mode of action of lysozyme.
本文试图描述理论方法在药物设计各个方面及相关问题中的应用范围、局限性和未来前景。量子力学和统计物理学（蒙特卡罗方法、分子动力学方法）这两种方法被用于评估诸如孤立分子及其自缔合体的电子密度分布、结构和构象、分子间相互作用等性质，以及与环境（如溶剂、受体分子）的相互作用。此类计算的有效性取决于诸如几何优化、相关能以及波函数形式的不同近似等因素，氮杂环的烯醇 - 酮互变异构现象的例子说明了这一点，该现象与一些核苷类似物的生物学（包括化疗）活性相关。对嘌呤和嘧啶评估了分子间相互作用，包括溶剂的作用。分子动力学方法的应用范围以其在溶菌酶作用模式中的应用为例进行了说明。
