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Predicting Molecular Crowding Effects in Ion–RNA Interactions

Yu, Tao, Zhu, Yuhong, He, Zhaojian, Chen, Shi-Jie
The Journal of physical chemistry 2016 v.120 no.34 pp. 8837-8844
Gibbs free energy, RNA, electrostatic interactions, ions, models, physical chemistry, prediction, solvents
We develop a new statistical mechanical model to predict the molecular crowding effects in ion–RNA interactions. By considering discrete distributions of the crowders, the model can treat the main crowder-induced effects, such as the competition with ions for RNA binding, changes of electrostatic interaction due to crowder-induced changes in the dielectric environment, and changes in the nonpolar hydration state of the crowder–RNA system. To enhance the computational efficiency, we sample the crowder distribution using a hybrid approach: For crowders in the close vicinity of RNA surface, we sample their discrete distributions; for crowders in the bulk solvent away from the RNA surface, we use a continuous mean-field distribution for the crowders. Moreover, using the tightly bound ion (TBI) model, we account for ion fluctuation and correlation effects in the calculation for ion–RNA interactions. Applications of the model to a variety of simple RNA structures such as RNA helices show a crowder-induced increase in free energy and decrease in ion binding. Such crowding effects tend to contribute to the destabilization of RNA structure. Further analysis indicates that these effects are associated with the crowder–ion competition in RNA binding and the effective decrease in the dielectric constant. This simple ion effect model may serve as a useful framework for modeling more realistic crowders with larger, more complex RNA structures.