Kabir Anowarul, Bhattarai Manish, Rasmussen Kim Ø, Shehu Amarda, Usheva Anny, Bishop Alan R, Alexandrov Boian S
Theoretical Division, Los Alamos National Laboratory, Los Alamos, 87544, NM, 87102.
George Mason University, 4400 University Dr, Fairfax, VA 22030.
bioRxiv. 2023 Sep 12:2023.09.09.557010. doi: 10.1101/2023.09.09.557010.
The two strands of the DNA double helix locally and spontaneously separate and recombine in living cells due to the inherent thermal DNA motion.This dynamics results in transient openings in the double helix and is referred to as "DNA breathing" or "DNA bubbles." The propensity to form local transient openings is important in a wide range of biological processes, such as transcription, replication, and transcription factors binding. However, the modeling and computer simulation of these phenomena, have remained a challenge due to the complex interplay of numerous factors, such as, temperature, salt content, DNA sequence, hydrogen bonding, base stacking, and others.
We present pyDNA-EPBD, a parallel software implementation of the Extended Peyrard-Bishop- Dauxois (EPBD) nonlinear DNA model that allows us to describe some features of DNA dynamics in detail. The pyDNA-EPBD generates genomic scale profiles of average base-pair openings, base flipping probability, DNA bubble probability, and calculations of the characteristically dynamic length indicating the number of base pairs statistically significantly affected by a single point mutation using the Markov Chain Monte Carlo (MCMC) algorithm.
由于DNA固有的热运动，DNA双螺旋的两条链在活细胞中会局部自发分离并重新结合。这种动力学导致双螺旋中出现瞬时开口，被称为“DNA呼吸”或“DNA气泡”。形成局部瞬时开口的倾向在广泛的生物过程中很重要，如转录、复制和转录因子结合。然而，由于众多因素（如温度、盐含量、DNA序列、氢键、碱基堆积等）之间复杂的相互作用，对这些现象进行建模和计算机模拟仍然是一个挑战。
我们展示了pyDNA-EPBD，这是扩展的佩亚尔德-毕晓普-多索瓦（EPBD）非线性DNA模型的并行软件实现，它使我们能够详细描述DNA动力学的一些特征。pyDNA-EPBD使用马尔可夫链蒙特卡罗（MCMC）算法生成平均碱基对开口、碱基翻转概率、DNA气泡概率的基因组规模图谱，以及计算特征动态长度，该长度表示受单点突变统计上显著影响的碱基对数量。
