论文标题
从头开始使用基于物理原子的自由能模型的核酸折叠模拟
Ab Initio Nucleic Acid Folding Simulations Using a Physics-Based Atomistic Free Energy Model
论文作者
论文摘要
进行核酸折叠的全分辨率原子模拟对生物分子建模仍然是一个挑战。了解核酸如何折叠以及它们如何在展开和重新折叠时如何在不同的折叠结构之间过渡具有重要意义。本文报告了倒置重复序列的Ab intibil折叠的理论模型和计算机模拟。该公式基于通过链闭合糖磷酸主链的全原子构象模型，它结合了三个主要的分子级驱动力 - 基础堆叠，反式诱导的主链自我互动和基础配对 - 通过独立的分析理论，旨在捕获和复制溶液的效果而无需进行液位水和simution simution simution simution and imputions insions insion insion insion insions insions insion insion insion ions ions ions ions ions ions效果。为了加速计算吞吐量，将用于计算骨架构象体积计算的混合数值/分析算法纳入了蒙特卡洛模拟中，并采用了特殊的随机抽样技术来实现从scratch折叠核酸折叠核酸的计算效率。本文介绍了实施细节，基准结果以及这种方法的优势和技术挑战。
Performing full-resolution atomistic simulations of nucleic acid folding has remained a challenge for biomolecular modeling. Understanding how nucleic acids fold and how they transition between different folded structures as they unfold and refold has important implications for biology. This paper reports a theoretical model and computer simulation of the ab initio folding of DNA inverted repeat sequences. The formulation is based on an all-atom conformational model of the sugar-phosphate backbone via chain closure, and it incorporates three major molecular-level driving forces - base stacking, counterion-induced backbone self-interactions and base pairing - via separate analytical theories designed to capture and reproduce the effects of the solvent without requiring explicit water and ions in the simulation. To accelerate computational throughput, a mixed numerical/analytical algorithm for the calculation of the backbone conformational volume is incorporated into the Monte Carlo simulation, and special stochastic sampling techniques were employed to achieve the computational efficiency needed to fold nucleic acids from scratch. This paper describes implementation details, benchmark results and the advantages and technical challenges with this approach.
