Physics MS Thesis Defense by Armin Hodaei

KOÇ UNIVERSITY

GRADUATE SCHOOL OF SCIENCES & ENGINEERING

PHYSICS

MS THESIS DEFENSE BY ARMIN HODAEI

Title: Mode-coupling analysis of allosteric interactions in Ack1

Speaker: Armin Hodaei

Time: August 9th, 2018, 14:00

Place: ENG B29

Koç University

Rumeli Feneri Yolu

Sariyer, Istanbul

Thesis Committee Members:

Assoc. Prof. Alkan Kabakçıoğlu (Advisor, Koç University)

Assoc. Prof. Mehmet Sayar (Koç University)

Asst. Prof. Neşe Aral (Türkisch-Deutsche Universität)

Abstract:

We investigate allostery in ACK1 (a protein important for cancer research) by means of a recently proposed model which takes into account the nonlinear aspect of the native configurational distribution of the protein. The model we employ exploits an analytical formulation based on the physical picture that allosteric interactions communicate through coupling between vibrational modes of the system (hence the nonlinear analysis). It has been shown to predict allosterically relevant loci on several proteins. The input is the trajectories of full atomistic molecular dynamics of the equilibrium structure obtained using AMBER package with ff14sb force-field, which are long enough (>100ns) to capture the nonlinear aspects of the distribution function.

The output of this analysis is a score assigned to each amino acid reflecting its relevance to mode-coupling. We observe that the sites with high mode-coupling score correlate well with the functional sites on the ACK1 protein. These findings may have therapeutic implications since ACK1 takes part as a signaling node that represents a possible target in cancer treatment. In several stages of cancer for instance in breast cancer, Ack1 promotes the phosphorylation and activation of Akt, an important mediator of signaling pathways that lead to transformation to cancer cells.