Author ORCID Identifier

Year of Publication


Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation


Arts and Sciences



First Advisor

Dr. Peter M. Kekenes-Huskey


Ca2+ is an important messenger that affects almost all cellular processes. Ca2+ signaling involves events that happen at various time-scales such as Ca2+ diffusion, trans-membrane Ca2+ transport and Ca2+-mediated protein-protein interactions. In this work, we utilized multi-scale computational methods to quantitatively characterize Ca2+ diffusion efficiency, Ca2+ binding thermodynamics and molecular bases of Ca2+-dependent protein-protein interaction. Specifically, we studied 1) the electrokinetic transport of Ca2+ in confined sub-µm geometry with complicated surfacial properties. We characterized the effective diffusion constant of Ca2+ in a cell-like environment, which helps to understand the spacial distribution of cytoplasmic Ca2+. 2) the association kinetics and activation mechanism of the protein phosphatase calcineurin (CaN) by its activator calmodulin (CaM) in the presence of Ca2+. We found that the association between CaM and CaN peptide is diffusion-limited and the rate could be tuned by charge density/distribution of CaN peptite. Moreover, we proposed an updated CaM/CaN interaction model in which a secondary interaction between CaN’s distal helix motif and CaM was highlighted. 3) the roles of Mg2+ and K+ in the active transport of Ca2+ by sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump. We found that Mg2+ most likely act as inhibitor while K+ as agonist in SERCA’s transport process of Ca2+. Results reported in this work shed insights into various aspects of Ca2+ signaling from molecular to cellular level.

Digital Object Identifier (DOI)

Funding Information

Maximizing Investigators’ Research Award (MIRA) (R35) from the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) under Grant R35GM124977 (09/01/17-08/31/22)