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Jung-Hsin Lin

2012-01-06
13:20:00 - 14:10:00

101 , Mathematics Research Center Building (ori. New Math. Bldg.)

In the beginning of the talk, I will give a brief history account for the development of theory for electrolyte solutions, with a focus on the Poisson-Boltzmann theory for strong electrolytes. I will then talk about some examples that can be dealt with Poisson-Boltzmann (PB) theory, and also some examples that need to go beyond PB by, e.g., molecular dynamics simulations:

One example that can be dealt with PB is the membrane association of Protein kinase C (PKC) family members, which are known to be allosterically activated following membrane recruitement by specific membrane-targeting modules. Conventional PKC isozymes are recruited to membranes by two such modules: a C1 domain, which binds diacylglycerol (DAG), and a C2 domain, which is a Ca2+-triggered phospholipid-binding module. In contrast, novel PKC isozymes respond only to DAG, despite the presence of a C2 domain. To understand why different isotypes of PKC C2 domains have so drastically different interactions with the cell membranes, we adopted a multi-scale approach to model the small unilamella vesicle and performed Poisson-Boltzmann calculations for the interactions between the C2 domains and the vesicle. We showed that PKCδ and a conventional isozyme, PKCβII, bind to anionic membranes with distinct mechanisms. We found out, although the C2 domain is a major determinant in driving the interaction of PKCβII with membranes, the C2 domain of PKCδ does not bind membranes. Instead, the C1B domain is the determinant that drives the association of PKCδ with the anionic membranes.

One example that apparently cannot be dealt with by PB is the folding of telomeric quadruplexes. Human telomeres are guanine rich DNA sequences. In vitro evidences show a high probability that a guanine rich DNA sequences folds into a quadruplex. Quadruplexes also act as conformational switches sensitive to the types of electrolyte ions in the solution. We have studied the structural properties and the folding process of the G-quadruplex by applying the molecular dynamics (MD) simulation and the targeted MD simulation methods to the system of a hybrid-I type G-quadruplex solvated in K+ solution, starting from the anti-parallel structure that should be stable in Na+ solution. Our simulations show that the channel K+ ions are very important to the stability of the G-quadruplex structure. At least one K+ ion is required to be in the quadruplex channel to maintain the G-quadruplex structure. G-quadruplex with no K+ ion in the channel unfolded in the simulations. In the folding process, K+ ions are incorporated to the core part of the G-quadruplex structure. At least one K+ should be incorporated to the channel pore during the folding process to maintain the stability of the structure. Each type of the G-quadruplex has a specific configuration of the conformation of the nucleotide bases of guanines. The targeted MD simulation studies of the folding process show that the nucleotide bases of guanine should alter to the right conformation at the early stage of the folding process.

For material related to this talk, click here.