Complete inhibition of a polyol nucleation by a micromolar biopolymer additive
Abstract
Preventing spontaneous crystallization of supersaturated solutions by additives is of critical interest to successful process design and implementation, with numerous applications in chemical, pharmaceutical, medical, pigment, and food industries, but challenges remain in laboratory and industry settings and fundamental understanding is lacking. When copresented with antifreeze proteins (AFPs), otherwise spontaneously crystallizing osmolytes are maintained at high supersaturations for months in over-wintering organisms. Thus, we here explore the inhibition phenomenon by AFPs, using persistent crystallization of a common sugar alcohol, D-mannitol, as a case study. We report experimentally that DAFP1, an insect AFP, completely inhibits D-mannitol nucleation. Computer simulations reveal a new mechanism for crystallization inhibition where the population of the crystal-forming conformers are selectively bound and randomized in solution by hydrogen bonding to the protein surface. These results highlight the advantages of using natural polymers to address crystallization inhibition challenges and suggest new strategies in controlling the nucleation processes.
Additional Information
© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Received 11 October 2021, Revised 14 November 2021, Accepted 16 December 2021, Available online 11 January 2022. Experimental portions of this work were performed at California State University, Los Angeles. We would like to thank Prof. Yin Yeh at the University of California, Davis for AFGPs, Prof. John Duman at University of Notre Dame for cDNA of DAFP1, and Dr. Ignacio Martini and Dr. Robert Taylor at the University of California, Los Angeles, for molecular instruments supported by the National Institutes of Health – the National Center for Research Resources under S10-RR025631. X.W. acknowledges supports from the National Institutes of Health (NIH grant number SC3GM086249) and the National Science Foundation (NSF grant number 1840835). A.K. acknowledges supports from NIH MARC U∗STAR (T34GM008228) and NSF LSAMP-BD (HRD-1700556) at Cal State LA. WAG acknowledges support from NSF (CBET-2005250). T.A.P. also acknowledges fruitful discussions and support from N.M., L.F.P., and V.A.P. and support from the JSOE startup fund at UCSD. This research was partially supported by NSF through the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC DMR-2011924). Computational support for this work was provided in part by the National Energy Research Scientific Computing Center (NERSC), a U.S. Department of Energy Office of Science User Facility operated under Contract No. DE-AC02-05CH11231. Theoretical portions of work were performed as a user project at the Molecular Foundry, Lawrence Berkeley National Laboratory supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under the same contract. This work also used the Extreme Science and Engineering Discovery Environment (XSEDE) from allocation DDP381 on the Comet and Expanse supercomputers at the San Diego Supercomputing center, which is supported by National Science Foundation grant number ACI-1548562. Author contributions. X.W. and S.W. conceived the idea. X.W. directed the protein studies. Y.B. and A.K. performed the protein studies. S.W. and X.W. directed and performed crystallization and solids characterization studies. A.L.R. directed X-ray crystallography studies. J.A.G. and A.L.R. performed X-ray crystallography studies. T.A.P. directed the computational and theoretical studies, S.K.K. performed the ligand docking studies, R.R. performed the quantum calculations, and L.B. performed the MD simulations. X.W., T.A.P., and W.A.G. drafted the manuscript. All authors discussed the results and commented on the manuscript. The authors declare no competing interests. Data and code availability. The data that support the findings of this study will be made available over the web. In-house programs that implement the two-phase thermodynamics method are available from the corresponding authors upon request. Modification to the LAMMPS simulation engine used in this study will be submitted to the original developers for inclusion in the official release.Attached Files
Published - 1-s2.0-S2666386421004537-main.pdf
Accepted Version - nihms-1781668.pdf
Supplemental Material - 1-s2.0-S2666386421004537-mmc1.pdf
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Additional details
- PMCID
- PMC8903182
- Eprint ID
- 112842
- Resolver ID
- CaltechAUTHORS:20220112-355642683
- S10-RR025631
- National Center for Research Resources
- SC3GM086249
- NIH
- CNS-1840835
- NSF
- T34GM008228
- NIH Predoctoral Fellowship
- HRD-1700556
- NSF
- CBET-2005250
- NSF
- University of California, San Diego
- DMR-2011924
- NSF
- DE-AC02-05CH11231
- Department of Energy (DOE)
- ACI-1548562
- NSF
- Created
-
2022-01-12Created from EPrint's datestamp field
- Updated
-
2022-10-12Created from EPrint's last_modified field
- Other Numbering System Name
- WAG
- Other Numbering System Identifier
- 1532