Modeling of nucleic acid complexes with cationic ligands: a specialized molecular mechanics force field and its application.
Modeling of nucleic acid complexes with cationic ligands: a specialized molecular mechanics force field and its application.
复制标题
具有阳离子配体的核酸复合物的建模：专门的分子力学力场及其应用。
DOI：
10.1080/07391102.1991.10507875
复制
发表时间：
1991
影响因子：
4.4
通讯作者：
Wilson,WD
中科院分区：
文献类型：
--
作者：
Veal,JM;Wilson,WD
提出了一种用于模拟核酸，特别是它们与阳离子配体的复合物的势能力场。力场是由Weiner，S. J.开发的力场的修改版本，Kollman，P.A.，Nguyen，D.T.还有地方检察官凯斯J.Comp.Chem.7，230-252（1986），并且基于使用依赖于距离的介电常数ε= 4 π j和部分中和的磷酸盐来表示溶剂和抗衡离子。Weineret等人力场的变化包括额外的原子类型和对货车范德华、静电、氢键和扭转参数的修改。力场的分子建模测试情况下，提出了一些简单的小分子，以及尿嘧啶和苯二聚，胸腺嘧啶腺嘌呤和胞嘧啶鸟嘌呤碱基对的形成，和腺苷/脱氧腺苷伪旋转。几个DNA和RNA寡聚体和DNA/RNA嵌入复合物与乙锭也建模与力场。在所有情况下，建模结果与现有的实验结果相比，毫不逊色。此外，通过NMR和X-射线晶体学技术实验观察到的核酸构象趋势再现。乙锭插层的建模结果表明，一个复杂的，其中有利的相互作用主要是货车德瓦尔斯接触，其中静电相互作用是一个相对较小的组件。我们觉得力场是特别有用的分子力学辅助药物设计，和分析的建模结果与设计的药物，选择性地结合到RNA。
A potential energy force field designed for modeling nucleic acids and particularly their complexes with cationic ligands is presented. The force field is a modified version of that developed by Weiner, S.J., Kollman, P.A., Nguyen, D.T. and Case, D.A.,J. Comp. Chem. 7, 230–252 (1986) and is based upon the use of a distance dependent dielectric constant, ϵ=4rij, and partially neutralized phosphates to represent solvent and counterion. Changes from the Weineret al.force field include additional atom types and modifications to van der Waals, electrostatic, hydrogen bonding and torsional parameters. Molecular modeling test cases of the force field are presented for a number of simple small molecules, as well as uracil and benzene dimerization, thymine-adenine and cystosine-guanine base pair formation, and adenosine/deoxyadenosine pseudorotation. Several DNA and RNA oligomers and DNA/RNA intercalation complexes with ethidium are also modeled with the force field. In all cases, the modeling results compare favorably with available experimental results. Additionally, conformational trends observed experimentally for nucleic acids by NMR and X-ray crystallographic techniques are reproduced. The modeling results for ethidium intercalation indicate a complex in which the favorable interactions are primarily van der Waals contacts, and in which electrostatic interactions are a relatively minor component. We feel the force field is particularly useful for molecular mechanics aided drug design, and an analysis of modeling results with respect to design of drugs which bind selectively to RNA is presented.