The alternative splicing during gene expression is regulated by a type of proteins called splicing factors. Recently, a splicing factor SF protein was formed to recognize guanines and cytosines at the binding site of the RNA segment. A series of mutations were performed on SF to understand the binding interactions of the protein and RNA. However, the change of binding interactions at the atomistic level due to the mutations have not been revealed. Here, we used molecular dynamics simulations to investigate the conformational changes due to the series of mutations. An example of the equilibrated conformations before and after a mutation is shown in the figure below. The left column is the binding configuration before the mutation, and the right column is the binding configuration after the mutation. In addition, we used the free energy perturbation theory to examine the free energy changes for the mutations. Our simulations show consistency with the experimental findings and reveal the details of molecular dynamics at the binding sites due to the mutations. Our results provide new insights on understanding the interaction between the splicing factor proteins and the RNA, which can be linked to understanding the pathogen of cancer and HIV.

Understanding protein-RNA interactions for alternative splicing during gene expression using molecular dynamic simulations

248th National Meeting (2014)

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