Computational structural analysis of signaling proteins: elucidating function and specificity

Abstract

I aim to develop computational tools to characterize nucleotide binding-proteins (NBPs) by a structural comparison of a sub-family. I am interested in how distinct structural subdomains combine to achieve complex function in a signaling pathway. Furthermore, I seek to reveal how differences in specific NBPs’ subdomains result in altered function and specificity by searching for commonalities and differences in their electrostatic and physico-chemical properties. This will enhance the detailed understanding of cellular signaling and provide a scientific basic for improved, target-specific therapeutics. My experimental background familiarized me with the significant questions facing the signal transduction field. However, I have felt limited by using ‘off the shelf’ software to complement my experimental efforts. In the Honig lab, a world leader in developing computational tools, I can learn to develop and utilize software that combine physical chemistry, bioinformatics and biophysics (notably, protein electrostatics). My experimental background and familiarity with the relevant signaling biology will enable me to develop and employ the relevant methods more effectively and better translate my conclusions to experimental applications. My current goal is to become an independent and successful researcher in the structural bioinformatic field. I wish to focus on problem-oriented research and gain insights that can direct experimental signal transduction research. My long-term goal is to return as an independent researcher to Israel and combine both worlds: explore protein families computationally and perform experimental work to prove or refute the hypotheses generated.