ORCID

http://orcid.org/0000-0003-1505-4805

Date of Award

Winter 12-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Physics

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Intrinsically disordered proteins and regions (IDPs / IDRs) are a class of proteins with diverse conformational heterogeneity that do not fold into a tertiary structure due to the lack of a native structural state. Consequently, disordered proteins are remarkably flexible and exhibit multivalent properties that enable them to adopt myriad functional roles within the cell such as: signaling transduction, transcription, enzymatic catalysis, translation, and many more. Due to their multivalency, some IDPs undergo monomeric and heterotypic interactions which can drive phase separation. Such IDPs can form membraneless organelles with specific regulatory roles within the cell which include, but are not limited to: RNA storage, neurotransmission, and cell-cycle regulation. However, the driving forces behind these mechanisms are not well understood. Dysregulation of these roles through the introduction of sequence mutations or cellular stress can lead to the formation of protein aggregates that can detrimentally impact cellular function and ability. Thus, IDPs are also implicated in multiple diseases like Type II diabetes, numerous cancers, and several neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Therefore, there is keen interest to understand the sequence-determinants of IDPs and characterize properties of their conformational ensembles that inform their function. This thesis is focused on the development and application of computational tools that can characterize the spatiotemporal properties of IDP simulations, as well as classify and identify possible sequence-determinants of phase separation.

Language

English (en)

Chair and Committee

Anders E. Carlsson

Committee Members

Rohit V. Pappu

Download

Share

COinS