Esmaeeli Reza, Andal Benedict, Perez Alberto
Quantum Theory Project, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA.
Life (Basel). 2022 Feb 9;12(2):261. doi: 10.3390/life12020261.
The β subunit of DNA polymererase III is a DNA sliding clamp associated with increasing the processivity of DNA synthesis. In its free form, it is a circular homodimer structure that can accomodate double-stranded DNA in a nonspecific manner. An open state of the clamp must be accessible before loading the DNA. The opening mechanism is still a matter of debate, as is the effect of bound DNA on opening/closing kinetics. We use a combination of atomistic, coarse-grained, and enhanced sampling strategies in both explicit and implicit solvents to identify opening events in the sliding clamp. Such simulations of large nucleic acid and their complexes are becoming available and are being driven by improvements in force fields and the creation of faster computers. Different models support alternative opening mechanisms, either through an in-plane or out-of-plane opening event. We further note some of the current limitations, despite advances, in modeling these highly charged systems with implicit solvent.
DNA聚合酶III的β亚基是一种DNA滑动夹，与提高DNA合成的持续合成能力相关。在其游离形式下，它是一种环状同二聚体结构，能够以非特异性方式容纳双链DNA。在加载DNA之前，夹钳的开放状态必须是可及的。开放机制以及结合的DNA对开放/关闭动力学的影响仍是一个有争议的问题。我们在显式和隐式溶剂中结合使用原子、粗粒度和增强采样策略，以识别滑动夹中的开放事件。这种对大型核酸及其复合物的模拟正变得可行，并且受到力场改进和更快计算机的推动。不同模型支持通过面内或面外开放事件的替代开放机制。我们进一步指出，尽管取得了进展，但在用隐式溶剂对这些高电荷系统进行建模时，目前仍存在一些局限性。
