Tushar Modi | Searcharxiv

arXiv2021

Vibrational density of states capture the role of dynamic allostery in protein evolution

Previous studies of the flexibilities of ancestral proteins suggests that proteins evolve their function by altering their native state ensemble. Here we propose a more direct method of visualizing this by measuring the changes in the vibrational density of states (VDOS) of proteins as they evolve. Through analysis of VDOS profiles of ancestral and extant proteins we observe that $\beta$-lactamase and thioredoxins evolve by altering their density of states in the terahertz region. Particularly, the shift in VDOS profiles between ancestral and extant proteins suggests that nature utilize dynamic allostery for functional evolution. Moreover, we also show that VDOS profile of individual position can be used to describe the flexibility changes, particularly those without any amino acid substitution.

physics.bio-ph↗

arXiv2019

Information propagation in time through allosteric signaling

Naively, one expects the information communicated by an enzyme downstream within a signaling network, in which the enzyme is embedded, to grow monotonically with the enzyme's rate of product formation. However, here we observe that this does not necessarily hold true for allosterically regulated enzymes, often observed in signaling networks. In particular, we find that the mutual information between the catalytic sites of an allosterically regulated enzyme and a receiver protein downstream in the signaling pathway depends on the transition kinetics between the different allosterically regulated states of the enzyme and their respective rates of product formation. Surprisingly, our work implies that allosteric down-regulation of an enzyme's rate of product formation may not only be used as a way to silence itself, as one would normally expect. Rather, down-regulation may also be used to increase the information communicated by this enzyme to a receiver protein downstream in a signaling pathway.

physics.bio-ph↗