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theses

Molecular simulations have become an essential part in modern chemistry research. Due to the wide variety and complex nature of practical chemistry problems, the multiscale simulation approach, which attempts to solve problems at different scales using different level of theories, has been widely employed. In this dissertation, several practical applications of multiscale simulation methods to the study of RNA catalysis as well as some method development work are presented. In Chapters 3 and 4, detailed investigations using quantum mechanical methods on the transition state structures in native and catalyzed model reactions that mimic RNA self-cleavage are presented, which serve as a baseline for the following mechanistic studies on real catalytic RNAs. Chapter 5 presents an example of a holistic approach on a mechanistic problem in a real catalytic RNA, which is the hammerhead ribozyme. Quantum mechanical methods, classical simulations and hybrid quantum-classical calculations are employed together to resolve the controversial role of residue G12 in hammerhead ribozyme. Finally, in Chapter 6, method developments on an advanced sampling method called the multi-dimensional replica exchange method is presented and applied to two prototypical problems in biochemistry. Taken together, the work presented here provide new insights into the molecular-level mechanism of RNA catalysis, which is of fundamental importance to our understanding of the underlying chemical principles in life.

ETD_7780

Ph.D.

Includes bibliographical references

by Haoyuan Chen

doi:10.7282/T35141NF

ETD doctoral

The author owns the copyright to this work.