Mahalik J P, Hildebrandt B, Muthukumar M
Department of Polymer Science and Engineering, Department of Physics, University of Massachusetts, Amherst, MA 01003, USA.
J Biol Phys. 2013 Mar;39(2):229-45. doi: 10.1007/s10867-013-9316-x. Epub 2013 Apr 23.
We have performed Langevin dynamics simulations of a coarse-grained model of ejection of dsDNA from Φ29 phage. Our simulation results show significant variations in the local ejection speed, consistent with experimental observations reported in the literature for both in vivo and in vitro systems. In efforts to understand the origin of such variations in the local speed of ejection, we have investigated the correlations between the local ejection kinetics and the packaged structures created at various motor forces and chain flexibility. At lower motor forces, the packaged DNA length is shorter with better organization. On the other hand, at higher motor forces typical of realistic situations, the DNA organization inside the capsid suffers from significant orientational disorder, but yet with long orientational correlation times. This in turn leads to lack of registry between the direction of the DNA segments just to be ejected and the direction of exit. As a result, a significant amount of momentum transfer is required locally for successful exit. Consequently, the DNA ejection temporarily slows down exhibiting pauses. This slowing down occurs at random times during the ejection process, completely determined by the particular starting conformation created by prescribed motor forces. In order to augment our inference, we have additionally investigated the ejection of chains with deliberately changed persistence length. For less inflexible chains, the demand on the occurrence of large momentum transfer for successful ejection is weaker, resulting in more uniform ejection kinetics. While being consistent with experimental observations, our results show the nonergodic nature of the ejection kinetics and call for better theoretical models to portray the kinetics of genome ejection from phages.
我们对Φ29噬菌体中双链DNA（dsDNA）喷射的粗粒度模型进行了朗之万动力学模拟。我们的模拟结果显示局部喷射速度存在显著变化，这与文献中报道的体内和体外系统的实验观察结果一致。为了理解这种局部喷射速度变化的起源，我们研究了局部喷射动力学与在各种驱动力和链柔韧性下形成的包装结构之间的相关性。在较低的驱动力下，包装的DNA长度较短且结构更好。另一方面，在现实情况中典型的较高驱动力下，衣壳内的DNA结构存在明显的取向无序，但取向相关时间较长。这反过来导致即将被喷射的DNA片段方向与出口方向之间缺乏对齐。因此，为了成功出口，局部需要大量的动量传递。结果，DNA喷射暂时减慢并出现停顿。这种减慢在喷射过程中的随机时间发生，完全由规定驱动力产生的特定起始构象决定。为了加强我们的推断，我们还研究了具有故意改变的持久长度的链的喷射。对于柔韧性较小的链，成功喷射所需的大动量传递发生的要求较弱，导致喷射动力学更加均匀。虽然与实验观察结果一致，但我们的结果显示了喷射动力学的非遍历性质，并呼吁建立更好的理论模型来描述噬菌体基因组喷射的动力学。
