Reaction mechanisms of ribozymes (“RNA enzymes”) revealed by the first-principles molecular dynamics simulations are discussed. The calculations are performed on an RNA fragment as a model structure of the catalytic site of ribozymes, in the absence/presence of explicit solvent water molecules, leading us to understanding the detailed mechanisms and the catalytic roles of divalent cations and solvent in in vitro reaction. Two cations, which are bound to the O2’/O5’ atoms of the catalytic nucleotide, and a hydroxide ion involved in a solvation shell of the cation bonding to the O2’ atom are indicated to concertedly decrease the activation barrier. The entire structure of a ribozyme molecule is now being investigated by using QM/MM hybrid molecular dynamics simulation. The computational methodology mentioned here is applicable also to other biological macromolecular systems.
A cyanobacterial clock protein KaiC shows circadian cycling of the phosphorylation level in vitro. We first developed an observation-based model. The KaiC-KaiA complex formation consequently reduces free KaiA molecules, thereby may exert a negative feedback effect toward KaiC phosphorylation. However, this model was shown not to be adequate to generate the KaiC phosphorylation cycle. Then, we analyzed generalized models and determined necessary conditions to generate the cycle. Based on the result, we realized the observed pattern of the KaiC phosphorylation cycle and predicted an unknown state that lies between KaiC phosphorylation and the formation of the KaiC/KaiA complex.
To understand aging and lifespan at the gene level, the era is just coming. Which is lifespan due to the programming or circumstance’s factors? The outline of lifespan, in this review, will be given from the deterministic and stochastic views. In the near future, the biophysical approach such as structural biology and mathematical framework is needed to develop the study of aging and lifespan.