Exploring the Balance between Folding and Functional Dynamics in Proteins and RNA

International Journal of Molecular Sciences

Jovaun Jackson²  Kien Nguyen²  Paul Charles Whitford¹ 

[1] Department of Physics, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA;

关键词: tRNA;    molecular dynamics;    biomolecular stability;    ribosome;   

DOI  :  10.3390/ijms16046868

来源: mdpi

【 摘 要 】

As our understanding of biological dynamics continues to be refined, it is becoming clear that biomolecules can undergo transitions between ordered and disordered states as they execute functional processes. From a computational perspective, studying disorder events poses a challenge, as they typically occur on long timescales, and the associated molecules are often large (i.e., hundreds of residues). These size and time requirements make it advantageous to use computationally inexpensive models to characterize large-scale dynamics, where more highly detailed models can provide information about individual sub-steps associated with function. To reduce computational demand, one often uses a coarse-grained representation of the molecule or a simplified description of the energetics. In order to use simpler models to identify transient disorder in RNA and proteins, it is imperative that these models can accurately capture structural fluctuations about folded configurations, as well as the overall stability of each molecule. Here, we explore a class of simplified model for which all non-hydrogen atoms are explicitly represented. We find that this model can provide a consistent description of protein folding and native-basin dynamics for several representative biomolecules. We additionally show that the native-basin fluctuations of tRNA and the ribosome are robust to variations in the model. Finally, the extended variable loop in tRNA^Ile is predicted to be very dynamic, which may facilitate biologically-relevant rearrangements. Together, this study provides a foundation that will aid in the application of simplified models to study disorder during function in ribonucleoprotein (RNP) assemblies.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.