Orozco M, Laughton C A, Herzyk P, Neidle S
Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research Sutton, Surrey, United Kingdom.
J Biomol Struct Dyn. 1990 Oct;8(2):359-73. doi: 10.1080/07391102.1990.10507810.
This study analyses the influence that the nature of the dielectric constant has on the final structures obtained from in vacuo molecular mechanics calculations on a drug-DNA complex and compares these structures with the energy minimised complex including explicit solvent molecules. Minimisations have been performed on a proflavine-decanucleotide structure, where the drug was intercalated at the d(CpG) site of the d(GpApTpApCpGpApTpApC) decamer duplex, using two expressions for the dielectric constant: a distance-independent, epsilon ij = EPS, and a distance-dependent, epsilon ij = EPS*Rij, form and for values of EPS from 1 to 8. Significantly different structures are obtained for the distance-independent and the distance-dependent expressions of the dielectric constant. The use of a distance-independent dielectric constant leads to distorted structures, which are very sensitive to slight changes in the value of EPS. The use of a distance-dependent dielectric constant leads to less distorted and more stable structures. The effects on helical parameters are analysed in detail. The structures obtained for different values of EPS (within the distance-dependent formalism) seem to converge for values of EPS equal to 4 or greater. Based on these results a distance-dependent form of the dielectric with an EPS value of 4 is recommended in order to produce reliable refined nucleic acid structures by molecular mechanics. These conclusions have been supported by molecular-mechanics minimisation of the same structure with the inclusion of explicit water molecules and counter-ions.
本研究分析了介电常数的性质对通过药物 - DNA复合物的真空分子力学计算获得的最终结构的影响，并将这些结构与包含明确溶剂分子的能量最小化复合物进行比较。使用介电常数的两种表达式，对原黄素 - 十聚核苷酸结构进行了最小化处理，其中药物插入到d(GpApTpApCpGpApTpApC)十聚体双链体的d(CpG)位点，这两种表达式分别为：与距离无关的εij = EPS，以及与距离有关的εij = EPS*Rij形式，且EPS取值范围为1至8。对于介电常数的与距离无关和与距离有关的表达式，得到了显著不同的结构。使用与距离无关的介电常数会导致结构扭曲，这些结构对EPS值的微小变化非常敏感。使用与距离有关的介电常数会导致扭曲程度较小且更稳定的结构。详细分析了对螺旋参数的影响。对于不同EPS值（在与距离有关的形式体系内）获得的结构，在EPS值等于4或更大时似乎会收敛。基于这些结果，建议使用EPS值为4的与距离有关的介电常数形式，以便通过分子力学产生可靠的精制核酸结构。这些结论得到了在包含明确水分子和抗衡离子的情况下对相同结构进行分子力学最小化的支持。
