(507f) Molecular Simulations to Compute the Dimerization Free Energy of Interferon Regulatory Factor Proteins and Effects of Binding of Ligands on the Dimerization.

Interferon regulatory factor (IRF) are a family of transcription factor proteins that are involved in early cell response to viral infections. Aberrant dimerization activity of these proteins has been associated with numerous immunological diseases including diabetes and cancer. We have calculated the dimerization free energy of two IRF3 protein chains. Using Markov state modeling, we have identified best small molecule binders to these proteins. The effect of binding of these small molecules on the dimerization free energy of IRF3 protein chains is then studied to identify the best inhibitors of IRF3 dimerization. The results from our studies will be generally applicable to other protein systems as well.