Fast Method for Computing Chemical Potentials and Liquid–Liquid Phase Equilibria of Macromolecular Solutions
- 5 July 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Physical Chemistry B
- Vol. 120 (33), 8164-8174
- https://doi.org/10.1021/acs.jpcb.6b01607
Abstract
Chemical potential is a fundamental property for determining thermodynamic equilibria involving exchange of molecules, such as between two phases of molecular systems. Previously, we developed the fast Fourier transform (FFT)-based method for Modeling Atomistic Protein-crowder interactions (FMAP) to calculate excess chemical potentials according to the Widom insertion. Intermolecular interaction energies were expressed as correlation functions and evaluated via FFT. Here, we extend this method to calculate liquid-liquid phase equilibria of macromolecular solutions. Chemical potentials are calculated by FMAP over a wide range of molecular densities, and the condition for coexistence of low- and high-density phases is determined by the Maxwell equal-area rule. When benchmarked on Lennard-Jones fluids, our method produces an accurate phase diagram at 18% of the computational cost of the current best method. Importantly, the gain in computational speed increases dramatically as the molecules become more complex, leading to many orders of magnitude in speed up for atomistically represented proteins. We demonstrate the power of FMAP by reporting the first results for the liquid-liquid coexistence curve of γII-crystallin represented at the all-atom level. Our method may thus open the door to accurate determination of phase equilibria for macromolecular mixtures such as protein-protein mixtures and protein-RNA mixtures, that are known to undergo liquid-liquid phase separation, both in vitro and in vivo.Keywords
Funding Information
- National Institute of General Medical Sciences (GM118091, GM88187)
This publication has 52 references indexed in Scilit:
- ALS/FTD Mutation-Induced Phase Transition of FUS Liquid Droplets and Reversible Hydrogels into Irreversible Hydrogels Impairs RNP Granule FunctionNeuron, 2015
- Protein ‘drops’ may seed brain diseaseScience, 2015
- Protein droplets in the spotlightNature Reviews Molecular Cell Biology, 2015
- Phase Transition of Spindle-Associated Protein Regulate Spindle Apparatus AssemblyCell, 2015
- Liquid-Liquid Phase Separation in BiologyAnnual Review of Cell and Developmental Biology, 2014
- Beyond the Van Der Waals loop: What can be learned from simulating Lennard-Jones fluids inside the region of phase coexistenceAmerican Journal of Physics, 2012
- Active liquid-like behavior of nucleoli determines their size and shape in Xenopus laevis oocytesProceedings of the National Academy of Sciences of the United States of America, 2011
- Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/CondensationScience, 2009
- Direct calculation of liquid–vapor phase equilibria from transition matrix Monte Carlo simulationThe Journal of Chemical Physics, 2003
- Phase Diagram of Colloidal SolutionsPhysical Review Letters, 1996