Peptide Solubility Limits: Backbone and Side-Chain Interactions

Overview

Journal J Phys Chem B

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Feb 1

PMID 29384681

Citations 11

Authors

Rahul Sarma

Ka-Yiu Wong

Gillian C Lynch

B Montgomery Pettitt

Affiliations

Soon will be listed here.

Abstract

We calculate the solubility limit of pentapeptides in water by simulating the phase separation in an oversaturated aqueous solution. The solubility limit order followed by our model peptides (GGRGG > GGDGG > GGGGG > GGVGG > GGQGG > GGNGG > GGFGG) is found to be the same as that reported for amino acid monomers from experiment (R > D > G > V > Q > N > F). Investigation of dynamical properties of peptides shows that the higher the solubility of a peptide is, the lower the time spent by the peptide in the aggregated cluster is. We also demonstrate that fluctuations in conformation and hydration number of peptide in monomeric form are correlated with the solubility of the peptide. We considered energetic mechanisms and dynamical properties of interbackbone CO-CO and CO···HN interactions. Our results confirm that CO-CO interactions more than the interbackbone H-bonds are important in peptide self-assembly and association. Further, we find that the stability of H-bonded peptide pairs arises mainly from coexisting CO-CO and CO···HN interactions.

Citing Articles

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Workman R, Huang C, Lynch G, Pettitt B Biophys J. 2024; 123(12):1668-1675.

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Backbone interactions and secondary structures in phase separation of disordered proteins.

Li S, Zhang Y, Chen J Biochem Soc Trans. 2024; 52(1):319-329.

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References

Auton M, Rosgen J, Sinev M, Holthauzen L, Bolen D . Osmolyte effects on protein stability and solubility: a balancing act between backbone and side-chains. Biophys Chem. 2011; 159(1):90-9. PMC: 3166983. DOI: 10.1016/j.bpc.2011.05.012. View

Chang J, Lenhoff A, Sandler S . Solvation free energy of amino acids and side-chain analogues. J Phys Chem B. 2007; 111(8):2098-106. DOI: 10.1021/jp0620163. View

PAULING L, Corey R, BRANSON H . The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc Natl Acad Sci U S A. 1951; 37(4):205-11. PMC: 1063337. DOI: 10.1073/pnas.37.4.205. View

Best R, Zheng W, Mittal J . Correction to Balanced Protein-Water Interactions Improve Properties of Disordered Proteins and Non-Specific Protein Association. J Chem Theory Comput. 2015; 11(4):1978. PMC: 4737529. DOI: 10.1021/acs.jctc.5b00219. View

Spassov V, Yan L, Flook P . The dominant role of side-chain backbone interactions in structural realization of amino acid code. ChiRotor: a side-chain prediction algorithm based on side-chain backbone interactions. Protein Sci. 2007; 16(3):494-506. PMC: 2203320. DOI: 10.1110/ps.062447107. View

Shoulders M, Guzei I, Raines R . 4-chloroprolines: synthesis, conformational analysis, and effect on the collagen triple helix. Biopolymers. 2007; 89(5):443-54. PMC: 2802577. DOI: 10.1002/bip.20864. View

Canchi D, Garcia A . Backbone and side-chain contributions in protein denaturation by urea. Biophys J. 2011; 100(6):1526-33. PMC: 3059734. DOI: 10.1016/j.bpj.2011.01.028. View

Hu C, Kokubo H, Lynch G, Bolen D, Pettitt B . Backbone additivity in the transfer model of protein solvation. Protein Sci. 2010; 19(5):1011-22. PMC: 2868243. DOI: 10.1002/pro.378. View

Newberry R, Raines R . The n→π* Interaction. Acc Chem Res. 2017; 50(8):1838-1846. PMC: 5559721. DOI: 10.1021/acs.accounts.7b00121. View

10.

Newberry R, Raines R . A prevalent intraresidue hydrogen bond stabilizes proteins. Nat Chem Biol. 2016; 12(12):1084-1088. PMC: 5110370. DOI: 10.1038/nchembio.2206. View

11.

Case D, Cheatham 3rd T, Darden T, Gohlke H, Luo R, Merz Jr K . The Amber biomolecular simulation programs. J Comput Chem. 2005; 26(16):1668-88. PMC: 1989667. DOI: 10.1002/jcc.20290. View

12.

DeRider M, Wilkens S, Waddell M, Bretscher L, Weinhold F, Raines R . Collagen stability: insights from NMR spectroscopic and hybrid density functional computational investigations of the effect of electronegative substituents on prolyl ring conformations. J Am Chem Soc. 2002; 124(11):2497-505. DOI: 10.1021/ja0166904. View

13.

Lu X, Murphy R . Asparagine Repeat Peptides: Aggregation Kinetics and Comparison with Glutamine Repeats. Biochemistry. 2015; 54(31):4784-94. DOI: 10.1021/acs.biochem.5b00644. View

14.

Bartlett G, Choudhary A, Raines R, Woolfson D . n-->pi* interactions in proteins. Nat Chem Biol. 2010; 6(8):615-20. PMC: 2921280. DOI: 10.1038/nchembio.406. View

15.

Drake J, Pettitt B . Force field-dependent solution properties of glycine oligomers. J Comput Chem. 2015; 36(17):1275-85. PMC: 4450816. DOI: 10.1002/jcc.23934. View

16.

Patel A, Varilly P, Chandler D . Fluctuations of water near extended hydrophobic and hydrophilic surfaces. J Phys Chem B. 2010; 114(4):1632-7. PMC: 3173972. DOI: 10.1021/jp909048f. View

17.

Needham Jr T, PARUTA A, GERRAUGHTY R . Solubility of amino acids in pure solvent systems. J Pharm Sci. 1971; 60(4):565-7. DOI: 10.1002/jps.2600600410. View

18.

Tsai H, Reches M, Tsai C, Gunasekaran K, Gazit E, Nussinov R . Energy landscape of amyloidogenic peptide oligomerization by parallel-tempering molecular dynamics simulation: significant role of Asn ladder. Proc Natl Acad Sci U S A. 2005; 102(23):8174-9. PMC: 1149403. DOI: 10.1073/pnas.0408653102. View

19.

Perutz M, Pope B, Owen D, Wanker E, Scherzinger E . Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid beta-peptide of amyloid plaques. Proc Natl Acad Sci U S A. 2002; 99(8):5596-600. PMC: 122815. DOI: 10.1073/pnas.042681599. View

20.

Eisenberg D, McLachlan A . Solvation energy in protein folding and binding. Nature. 1986; 319(6050):199-203. DOI: 10.1038/319199a0. View