IMSc Webinar

The role of order and disorder in protein structure

Debayan Chakraborty

University of Texas at Austin

Biology is a fascinating story of order and disorder. The beautiful structures of single- and multi-domain proteins are clearly ordered in some fashion but cannot be readily classified using group theory methods that are successfully used to describe periodic crystals. For this reason, protein structures are considered to be aperiodic, and may have evolved this way for functional purposes, especially in instances that require a combination of softness and rigidity within the same molecule. By analyzing the solved protein structures, we show that orientational symmetry is broken in the aperiodic arrangement of the secondary structure elements (SSEs), which we deduce by calculating the nematic order parameter, P₂. We find that the folded structures are nematic droplets with a broad distribution of P₂. We argue that a non-zero value of P₂, leads to an arrangement of the SSEs that can resist external forces, which is a requirement for allosteric proteins.

The second half of my talk will highlight the role of disorder, in the context of intrinsically disordered proteins (IDPs), which are prone to aggregation. We show that the seeds of aggregation are encoded as excitations (N* states) within the monomer free energy spectrum of these IDPs. For Aβ40 and Aβ42, the two major isoforms implicated in Alzheimer’s disease, the free energy ground state corresponds to random coils (RCs), although a sparse population of aggregation- prone (N*) structures, resembling the monomer units within experimentally characterized fibril polymorphs, could be identified within the conformational ensemble. Interestingly, the N* theory also rationalizes the nearly one order of magnitude difference in the aggregation rates of Aβ40 and Aβ42.

The talk will be based on the following references:

(1) D. Chakraborty, M. L. Mugnai and D. Thirumalai, Symmetry, 13, 770, 2021.
(2) D. Chakraborty, J. E. Straub and D. Thirumalai, Proc. Natl. Acad. Sci. USA, 117, 19926, 2020.


Meeting link: zoom.us/j/95183490304?pwd=QmErZDRpeGtvYmZ2VnJWTDBOT3ZhQT09

Meeting ID: 951 8349 0304
Passcode: 849445