Sfyrakis Konstantinos, Provata Astero, Povey David C, Howlin Brendan J
School of Biomedical and Life Sciences, Chemistry, University of Surrey, GU2 7XH, Guildford, UK.
J Mol Model. 2004 Jun;10(3):185-97. doi: 10.1007/s00894-004-0182-0. Epub 2004 Mar 24.
A software algorithm has been developed to investigate the folding process in B-DNA structures in vacuum under a simple and accurate force field. This algorithm models linear double stranded B-DNA sequences based on a local, sequential minimization procedure. The original B-DNA structures were modeled using initial nucleotide structures taken from the Brookhaven database. The models contain information at the atomic level allowing one to investigate as accurately as possible the structure and characteristics of the resulting DNA structures. A variety of DNA sequences and sizes were investigated containing coding and non-coding, random and real, homogeneous or heterogeneous sequences in the range of 2 to 40 base pairs. The force field contains terms such as angle bend, Lennard-Jones, electrostatic interactions and hydrogen bonding which are set up using the Dreiding II force field and defined to account for the helical parameters such as twist, tilt and rise. A close comparison was made between this local minimization algorithm and a global one (previously published) in order to find out advantages and disadvantages of the different methods. From the comparison, this algorithm gives better and faster results than the previous method, allowing one to minimize larger DNA segments. DNA segments with a length of 40 bases need approximately 4 h, while 2.5 weeks are needed with the previous method. After each minimization the angles between phosphate-oxygen-carbon A1, the oxygen-phosphate-oxygen A2 and the average helical twists were calculated. From the generated fragments it was found that the bond angles are A1=150 degrees +/-2 degrees and A2=130 degrees +/-10 degrees, while the helical twist is 36.6 degrees +/-2 degrees in the A strand and A1=150 degrees +/-6 degrees and A2=130+/-6 degrees with helical twist 39.6 degrees +/-2 degrees in the B strand for the DNA segment with the same sequence as the Dickerson dodecamer.
已开发出一种软件算法，用于在简单且精确的力场下研究真空中B-DNA结构的折叠过程。该算法基于局部顺序最小化程序对线性双链B-DNA序列进行建模。最初的B-DNA结构使用从布鲁克海文数据库获取的初始核苷酸结构进行建模。这些模型包含原子水平的信息，使人们能够尽可能准确地研究所得DNA结构的结构和特征。研究了各种DNA序列和大小，包括2至40个碱基对范围内的编码和非编码、随机和真实、均匀或异质序列。力场包含诸如角弯曲、 Lennard-Jones、静电相互作用和氢键等项，这些项使用Dreiding II力场设置，并定义为考虑螺旋参数，如扭曲、倾斜和上升。为了找出不同方法的优缺点，将这种局部最小化算法与一种全局算法（先前已发表）进行了仔细比较。通过比较，该算法比先前的方法给出了更好、更快的结果，使人们能够最小化更大的DNA片段。长度为40个碱基的DNA片段大约需要4小时，而使用先前的方法则需要2.5周。每次最小化后，计算磷酸-氧-碳A1、氧-磷酸-氧A2之间的角度以及平均螺旋扭曲。从生成的片段中发现，对于与Dickerson十二聚体具有相同序列的DNA片段，A链中的键角为A1 = 150度±2度，A2 = 130度±10度，螺旋扭曲为36.6度±2度；B链中的A1 = 150度±6度，A2 = 130±6度，螺旋扭曲为39.6度±2度。
