Lafontaine I, Lavery R
Laboratoire de Biochimie Théorique UPR 9080 Centre National de la Recherche Scientifique, Institut de Biologie Physico-Chimique, Paris 75005, France.
Biophys J. 2000 Aug;79(2):680-5. doi: 10.1016/S0006-3495(00)76326-0.
Base sequence influences the structure, mechanics, dynamics, and interactions of nucleic acids. However, studying all possible sequences for a given fragment leads to a number of base combinations that increases exponentially with length. We present here a novel methodology based on a multi-copy approach enabling us to determine which base sequence favors a given structural change or interaction via a single energy minimization. This methodology, termed ADAPT, has been implemented starting from the JUMNA molecular mechanics program by adding special nucleotides, "lexides," containing all four bases, whose contribution to the energy of the system is weighted by continuously variable coefficients. We illustrate the application of this approach in the case of double-stranded DNA by determining the optimal sequences satisfying structural (B-Z transition), mechanical (intrinsic curvature), and interaction (ligand-binding) properties.
碱基序列影响核酸的结构、力学、动力学及相互作用。然而，研究给定片段的所有可能序列会导致碱基组合数量随长度呈指数增长。我们在此提出一种基于多拷贝方法的新方法，使我们能够通过单次能量最小化来确定哪种碱基序列有利于特定的结构变化或相互作用。这种方法称为ADAPT，它是在JUMNA分子力学程序的基础上实现的，通过添加特殊的核苷酸“lexides”，其中包含所有四种碱基，其对系统能量的贡献由连续可变系数加权。我们通过确定满足结构（B-Z转变）、力学（固有曲率）和相互作用（配体结合）特性的最佳序列，来说明该方法在双链DNA中的应用。
