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Design of intrinsically disordered proteins that undergo phase transitions with lower critical solution temperatures

Authors :
Xiangze Zeng
Chengwen Liu
Martin J. Fossat
Pengyu Ren
Ashutosh Chilkoti
Rohit V. Pappu
Source :
APL Materials, Vol 9, Iss 2, Pp 021119-021119-13 (2021)
Publication Year :
2021
Publisher :
AIP Publishing LLC, 2021.

Abstract

Many naturally occurring elastomers are intrinsically disordered proteins (IDPs) built up of repeating units, and they can demonstrate two types of thermoresponsive phase behavior. Systems characterized by lower critical solution temperatures (LCSTs) undergo phase separation above the LCST, whereas systems characterized by upper critical solution temperatures (UCSTs) undergo phase separation below the UCST. There is congruence between thermoresponsive coil–globule transitions and phase behavior, whereby the theta temperatures above or below which the IDPs transition from coils to globules serve as useful proxies for the LCST/UCST values. This implies that one can design sequences with desired values for the theta temperature with either increasing or decreasing radii of gyration above the theta temperature. Here, we show that the Monte Carlo simulations performed in the so-called intrinsic solvation (IS) limit version of the temperature dependent self-Assembly of Biomolecules Studied by an Implicit, Novel, and Tunable Hamiltonian (ABSINTH) implicit solvation model yield a useful heuristic for discriminating between sequences with known LCST and UCST phase behavior. Accordingly, we use this heuristic in a supervised approach, integrate it with a genetic algorithm, combine this with IS limit simulations, and demonstrate that novel sequences can be designed with LCST phase behavior. These calculations are aided by direct estimates of temperature dependent free energies of solvation for model compounds that are derived using the polarizable atomic multipole optimized energetics for biomolecular applications forcefield. To demonstrate the validity of our designs, we calculate coil–globule transition profiles using the full ABSINTH model and combine these with Gaussian cluster theory calculations to establish the LCST phase behavior of designed IDPs.

Details

Language :
English
ISSN :
2166532X
Volume :
9
Issue :
2
Database :
Directory of Open Access Journals
Journal :
APL Materials
Publication Type :
Academic Journal
Accession number :
edsdoj.657d67dbca348dcb56a5c9da7c08d21
Document Type :
article
Full Text :
https://doi.org/10.1063/5.0037438