Skip to main content
SpringerLink
Log in

On the transferability of fractional contributions to the hydration free energy of amino acids

  • Regular Article
  • Published:
Theoretical Chemistry Accounts Aims and scope Submit manuscript

Abstract

This study reports the application of the quantum mechanical self-consistent reaction field MST method to compute the solvation profile in water of the twenty natural amino acids. The aim is to derive intrinsic fractional contributions to the hydration free energy and to examine their transferability to peptides. To this end, IEF-MST calculations have been performed at the B3LYP/6-31G(d) level for the series of acetyl amino acid amides, which were chosen as model compounds. In order to account for the flexibility of both the backbone and the side chain in deriving the hydration fractional contributions, calculations have been performed for representative conformers taken from the Dunbrack’s backbone-dependent conformational library. The results allow us to dissect the hydration free energy into backbone and side chain contributions and examine the conformational dependence of the fragmental contributions to hydration. For the backbone, different hydration contributions are found for α-helical and β-sheet conformations, which mainly reflect differences in the electrostatic contribution to hydration of the carbonyl group. In contrast, the conformational flexibility of the side chain is found to have little impact on the fractional contribution to hydration. These findings should be valuable to refine semiempirical methods for predicting solvation properties of peptides and proteins in large-scale genomic studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Pliska V, Schmidt M, Fauchere JL (1981) Partition coefficients of amino acids and hydrophobic parameters π of their side-chains as measured by thin-layer chromatography. J Chromatogr 216:79–92

    Article  CAS  Google Scholar 

  2. Fauchere JL, Pliska V (1983) Hydrophobic parameters-π of amino-acid side-chains from the partitioning of N-acetyl-amino-acid amides. Eur J Med Chem 18:369–375

    CAS  Google Scholar 

  3. Kim A, Szoka FC (1992) Amino-acid side-chain contributions to free energy of transfer of tripeptides from water to Octanol. Pharm Res 9:504–514

    Article  CAS  Google Scholar 

  4. Radzicka A, Wolfenden R (1988) Comparing the polarities of the amino acids—side-chain distribution coefficients between the vapor phase cyclohexane, 1-octanol and neutral aqueous solution. Biochemistry 27:1664–1670

    Article  CAS  Google Scholar 

  5. Radzicka A, Pedersen L, Wolfenden R (1988) Influences of solvent water on protein folding—free energies of solvation of cis and trans peptides are nearly identical. Biochemistry 27:4538–4541

    Article  CAS  Google Scholar 

  6. Wimley WC, Creamer TP, White SH (1996) Solvation energies of amino acid side chains and backbone in a family of host-guest pentapeptides. Biochemistry 35:5109–5124

    Article  CAS  Google Scholar 

  7. Auton M, Bolen DW (2004) Additive transfer free energies of the peptide backbone unit that are independent of the model compound and the choice of concentration scale. Biochemistry 43:1329–1342

    Article  CAS  Google Scholar 

  8. Shaytan AK, Shaitan KV, Khokhlov AR (2009) Solvent accessible surface area of amino acid residues in globular proteins: correlation of apparent transfer free energies with experimental hydrophobicity scales. Biomacromolecules 10:1224–1237

    Article  CAS  Google Scholar 

  9. Moon CP, Fleming KG (2011) Side-chain hydrophobicity scale derived from transmembrane protein folding into lipid bilayers. Proc Natl Acad Sci 108:10174–10177

    Article  CAS  Google Scholar 

  10. Gu W, Rahi SJ, Helms V (2004) Solvation free energies and transfer free energies for amino acids from hydrophobic solution to water solution from a very simple residue model. J Phys Chem B 108:5806–5814

    Article  CAS  Google Scholar 

  11. Villa A, Mark AE (2002) Calculation of the free energy of solvation for neutral analogs of amino acid side chains. J Comp Chem 23:548–553

    Article  CAS  Google Scholar 

  12. Shirts MR, Pitera JW, Swope WC, Pande VS (2003) Extremely precise free energy calculations of amino acid side chain analogs: comparison of common molecular mechanics force fields for proteins. J Chem Phys 119:5740–5761

    Article  CAS  Google Scholar 

  13. Deng YQ, Roux B (2004) Hydration of amino acid side chains: nonpolar and electrostatic contributions calculated from staged molecular dynamics free energy simulations with explicit water molecules. J Phys Chem B 108:16567–16576

    Article  CAS  Google Scholar 

  14. Ben-Naim A, Marcus Y (1984) Solvation thermodynamics of non-ionic solutes. J Chem Phys 81:2016–2027

    Article  CAS  Google Scholar 

  15. Tomasi J, Persico M (1994) Molecular interactions in solution: an overview of methods based on continuous distributions of the solvent. Chem Rev 94:2027–2094

    Article  CAS  Google Scholar 

  16. Gao J (1996) Hybrid quantum and molecular mechanical simulations: an alternative avenue to solvent effects in organic chemistry. Acc Chem Res 29:298–305

    Article  CAS  Google Scholar 

  17. Bashford D, Case DA (2000) Generalized born models of macromolecular solvation effects. Ann Rev Phys Chem 51:129–152

    Article  CAS  Google Scholar 

  18. Orozco M, Luque FJ (2000) Theoretical methods for the description of the solvent effect in biomolecular systems. Chem Rev 100:4187–4226

    Article  CAS  Google Scholar 

  19. Prabhu N, Sharp K (2006) Protein-solvent interactions. Chem Rev 106:1616–1623

    Article  CAS  Google Scholar 

  20. Cramer CJ, Truhlar DG (1999) Implicit solvation models: equilibria structure spectra and dynamics. Chem Rev 99:2161–2200

    Article  CAS  Google Scholar 

  21. Tomasi J, Mennucci B, Cammi R (2005) Quantum mechanical continuum solvation models. Chem Rev 105:2999–3093

    Article  CAS  Google Scholar 

  22. Guthrie JP (2009) A blind challenge for computational solvation free energies: introduction and overview. J Phys Chem B 113:4501–4507

    Article  CAS  Google Scholar 

  23. Geballe MT, Skillman AG, Nicholls A, Guthrie JP, Taylor PJ (2010) The SAMPL2 blind prediction challenge: introduction and overview. J Comput Aided Mol Des 24:259–279

    Article  CAS  Google Scholar 

  24. Soteras I, Forti F, Orozco M, Luque FJ (2009) Performance of the IEF-MST solvation continuum model in a blind test prediction of hydration free energies. J Phys Chem B 113:9330–9334

    Article  CAS  Google Scholar 

  25. Marenich AV, Cramer CJ, Truhlar DG (2009) Performance of SM6, SM8, and SMD on the SAMPL1 test set for the prediction of small-molecule solvation free energies. J Phys Chem B 113:4538–4543

    Article  CAS  Google Scholar 

  26. Klamt A, Eckert F, Diedenhofen M (2009) Prediction of the free energy of hydration of a challenging set of pesticide-like compounds. J Phys Chem B 113:4508–4510

    Article  CAS  Google Scholar 

  27. Soteras I, Orozco M, Luque FJ (2010) Performance of the IEF-MST solvation continuum model in the SAMPL2 blind test prediction of hydration and tautomerization free energies. J Comput-Aided Mol Des 24:281–291

    Article  CAS  Google Scholar 

  28. Ribeiro RF, Marenich AV, Cramer CJ, Truhlar DG (2010) Prediction of SAMPL2 aqueous solvation free energies and tautomeric ratios using the SM8, SM8AD, and SMD solvation models. J Comput-Aided Mol Des 24:317–333

    Article  CAS  Google Scholar 

  29. Klamt A, Diedenhofen M (2010) Blind prediction test of free energies of hydration with COSMO-RS. J Comput Aided Mol Des 24:357–360

    Article  CAS  Google Scholar 

  30. Jones S, Thornton JM (1997) Analysis of protein–protein interaction sites using surface patches. J Mol Biol 272:121–132

    Article  CAS  Google Scholar 

  31. Vonheijne G (1994) Membrane-proteins—from sequence to structure. Annu Rev Biophys Biomol Struct 23:167–192

    Article  CAS  Google Scholar 

  32. Bartlett GJ, Porter CT, Borkakoti N, Thornton JM (2002) Analysis of catalytic residues in enzyme active sites. J Mol Biol 324:105–121

    Article  CAS  Google Scholar 

  33. Eisenberg D, McLachlan AD (1986) Solvation energy in protein folding and binding. Nature 319:199–203

    Article  CAS  Google Scholar 

  34. Eisenberg D, Wilcox W, McLachlan AD (1986) Hydrophobicity and amphiphilicity in protein structure. J Cell Biochem 31:11–17

    Article  CAS  Google Scholar 

  35. Sippl MJ (1993) Boltzmann principle knowledge-based mean fields and protein folding—an approach to the computational determination of protein structures. J Comput Aided Mol Des 7:473–501

    Article  CAS  Google Scholar 

  36. Jackson RM, Sternberg MJE (1995) A continuum model for protein–protein interactions: application to the docking problem. J Mol Biol 250:258–275

    Article  CAS  Google Scholar 

  37. Lazaridis T, Karplus M (1999) Discrimination of the native from misfolded protein models with an energy function including implicit solvation. J Mol Biol 288:477–487

    Article  CAS  Google Scholar 

  38. Chang J, Lenhoff AM, Sandler SI (2007) Solvation free energy of amino acids and side-chain analogues. J Phys Chem B 111:2098–2106

    Article  CAS  Google Scholar 

  39. Morreale A, de la Cruz X, Meyer T, Gelpi JL, Luque FJ, Orozco M (2005) Partition of protein solvation into group contributions from molecular dynamics simulations. Proteins-Struct Funct Bioinf 58:101–109

    Article  CAS  Google Scholar 

  40. Morreale A, Gelpi JL, Luque FJ, Orozco M (2003) Continuum and discrete calculation of fractional contributions to solvation free energy. J Comput Chem 24:1610–1623

    Article  CAS  Google Scholar 

  41. Talavera D, Morreale A, Meyer T, Hospital A, Ferrer-Costa C, Gelpí JL, de la Cruz X, Soliva R, Luque FJ, Orozco M (2006) A fast method for the determination of fractional contributions to solvation in proteins. Prot Sci 15:2525–2533

    Article  CAS  Google Scholar 

  42. Arab S, Sadeghi M, Eslahchi C, Pezeshk H, Sheari A (2010) A pairwise residue contact area-based mean force potential for discrimination of native protein structure. BMC Bioinf 11:16

    Article  Google Scholar 

  43. Giesen DJ, Chamber CC, Cramer CJ, Truhlar DG (1997) What controls partitioning of the nucleic acid bases between chloroform and water? J Phys Chem B 101:5084–5088

    Article  CAS  Google Scholar 

  44. Hawkins GD, Cramer CJ, Truhlar DG (1998) Universal quantum mechanical model for solvation free energies based on gas-phase geometries. J Phys Chem B 102:3257–3271

    Article  CAS  Google Scholar 

  45. Hornig M, Klamt A (2005) COSMOfrag: a novel tool for high-throughput ADME property prediction and similarity screening based on quantum chemistry. J Chem Inf Model 45:1169–1177

    Article  CAS  Google Scholar 

  46. Thormann M, Klamt A, Hornig M, Almstetter M (2006) Cosmosim: bioisosteric similarity based on cosmo-RS σ profiles. J Chem Inf Model 46:1040–1053

    Article  CAS  Google Scholar 

  47. Luque FJ, Bofill JM, Orozco M (1995) New strategies to incorporate the solvent polarization in self-consistent reaction field and free-energy perturbation simulations. J Chem Phys 103:10183–10191

    Article  CAS  Google Scholar 

  48. Luque FJ, Barril X, Orozco M (1999) Fractional description of free energies of solvation. J Comput Aided Mol Des 13:139–152

    Article  CAS  Google Scholar 

  49. Muñoz J, Barril X, Hernandez B, Orozco M, Luque FJ (2002) Hydrophobic similarity between molecules: a MST-based hydrophobic similarity index. J Comput Chem 23:554–563

    Article  Google Scholar 

  50. Muñoz-Muriedas J, Perspicace S, Bech N, Guccione S, Orozco M, Luque FJ (2005) Hydrophobic molecular similarity from MSDT fractional contributions to the octanol/water partition coefficient. J Comput-Aided Mol Des 19:401–419

    Article  Google Scholar 

  51. Luque FJ, Curutchet C, Munoz-Muriedas J, Bidon-Chanal A, Soteras I, Morreale A, Gelpi JL, Orozco M (2003) Continuum solvation models: dissecting the free energy of solvation. J Comput Chem 5:3827–3836

    Google Scholar 

  52. Dunbrack JRL, Karplus M (1994) Conformational analysis of the backbone-dependent rotamer preferences of protein sidechains. Nat Struct Biol 1:334–340

    Article  CAS  Google Scholar 

  53. Dunbrack JRL, Karplus M (1993) Backbone-dependent rotamer library for proteins application to side-chain prediction. J Mol Biol 230:543–574

    Article  CAS  Google Scholar 

  54. Guha R, Howard MT, Hutchison GR, Murray-Rust P, Rzepa H, Steinbeck C, Wegner J, Willighagen EL (2006) The blue obelisk—interoperability in chemical informatics. J Chem Inf Model 46:991–998

    Article  CAS  Google Scholar 

  55. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235–242

    Article  CAS  Google Scholar 

  56. Johansson J, Szyperski T, Curstedt T, Wuthrich K (1994) The NMR structure of the pulmonary surfactant-associated polypeptide SP-C in an apolar solvent contains a valyl-rich alpha-helix. Biochemistry 33:6015–6023

    Article  CAS  Google Scholar 

  57. Garnett JA, Baumberg S, Stockley PG, Phillips SE (2007) A high-resolution structure of the DNA-binding domain or AhrC, the arginine repressor/activator protein fro Bacillus subtilis. Acta Crystallogr Sect F 63:914–917

    Article  Google Scholar 

  58. Kang BS, Devedjiev Y, Derewenda U, Derewenda ZS (2004) The PDZ2 domain of syntenin at ultra-high resolution: bridging the gap between macromolecular and small molecule crystallography. J Mol Biol 338:483–493

    Article  CAS  Google Scholar 

  59. Sauer F, Wilmanns M. doi:10.2210/pdb3puc/pdb

  60. Curutchet C, Orozco M, Luque FJ (2001) Solvation in octanol: parametrization of the continuum MST model. J Comput Chem 22:1180–1193

    Article  CAS  Google Scholar 

  61. Soteras I, Curutchet C, Bidon-Chanal A, Orozco M, Luque FJ (2005) Extension of the MST model to the IEF formalism: HF and B3LYP parametrizations. J Mol Struct Theochem 727:29–40

    Article  CAS  Google Scholar 

  62. Cancès E, Mennucci B, Tomasi J (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J Chem Phys 107:3032–3041

    Article  Google Scholar 

  63. Pierotti RA (1976) Scaled particle theory of aqueous and non-aqueous solutions. Chem Rev 76:717–726

    Article  CAS  Google Scholar 

  64. Gaussian 03 Revision C02 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JJA, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2004) Gaussian Inc, Wallingford CT

  65. Case DA, Darden TA, Cheatham TE, Simmerling CL, Wang J, Duke RE, Luo R, Walker RC, Zhang W, Merz KM, Roberts BP, Wang B, Hayik S, Roitberg A, Seabra G, Kolossváry I, Wong KF, Paesani F, Vanicek J, Liu J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Cai Q, Ye X, Wang J, Hsieh HJ, Cui G, Roe DR, Mathews DH, Seetin MG, Sagui C, Babin V, Luchko T, Gusarov S, Kovalenko A, Kollman PA (2010) AMBER 11

  66. Massart DL, Vandeginste BGM, Buydens LMC, De Jong S, Lewi PJ, Smeyers-Verbeke J (1998) In handbook of chemometrics and qualimetrics. Elsevier Science, Amsterdam

    Google Scholar 

  67. R-Development Core Team (2011) R: a language and environment for statistical computing. http://www.r-project.org (accessed 2011)

  68. Deelman E, Gannon D, Shields M, Taylor I (2009) Workflows and e-science: an overview of workflow system features and capabilities. Future Gener Comput Syst 25:528–540

    Article  Google Scholar 

  69. Altintas I, Berkley C, Jaeger E, Jones M, Ludäscher B, Mock S (2004) In Kepler: an extensible system for design and execution of scientific workflows. In: Proceedings of the international conference on scientific and statistical database management SSDBM, vol 16, pp 423–424

  70. Wolfenden R, Andersson L, Cullis PM, Southgate CCB (1981) Affinities of amino acid side chains for solvent water. Biochemistry 20:849–855

    Article  CAS  Google Scholar 

  71. Smith BJ (1999) Solvation parameters for amino acids. J Comput Chem 20:428–442

    Article  CAS  Google Scholar 

  72. Shirts MR, Pande VS (2005) Solvation free energies of amino acid side chain analogs for common molecular mechanics water models. J Chem Phys 122:134508

    Article  Google Scholar 

  73. Avbelj F (2000) Amino acid conformational preferences and solvation of polar backbone atoms in peptides and proteins. J Mol Biol 300:1335–1359

    Article  CAS  Google Scholar 

  74. Lin B, Pettitt BM (2011) Electrostatic solvation free energy of amino acid side chain analogs: implications for the validity of electrostatic linear response in water. J Comput Chem 32:878–885

    Article  CAS  Google Scholar 

  75. Baldwin RL (2002) Relation between peptide backbone solvation and the energetics of peptide hydrogen bonds. Biophys Chem 101:203–210

    Article  Google Scholar 

  76. Gould IR, Cornell WD, Hillier IH (1994) A quantum mechanical investigation of the conformational energetics of the alanine and glycine dipeptides in the gas phase and in aqueous solution. J Am Chem Soc 116:9250–9256

    Article  CAS  Google Scholar 

  77. Beachy MD, Chasman D, Murphy RB, Halgren TA, Friesner RA (1997) Accurate ab initio quantum chemical determination of the relative energetics of peptide conformations and assessment of empirical force fields. J Am Chem Soc 119:5908–5920

    Article  CAS  Google Scholar 

  78. Staritzbichler R, Gu W, Helms V (2005) Are solvation free energies of homogeneous helical peptides additive? J Phys Chem B 109:19000–19007

    Article  CAS  Google Scholar 

  79. Avbelj F, Baldwin RL (2009) Origin of the change in solvation enthalpy of the peptide group when neighboring peptide groups are added. Proc Natl Acad Sci USA 106:3137–3141

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Dr. Carles Curutchet is acknowledged for his assistance. This work was supported by the Spanish Ministerio de Innovación y Ciencia (SAF2011-27642 and “Juan de la Cierva” contract granted to JMC) and the Generalitat de Catalunya (2009-SGR00298 and XRQTC). Computational facilities provided by the Centre de Supercomputació de Catalunya are acknowledged.

Author information

Authors and Affiliations

  1. Department of Physical Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Campus de l’Alimentació Torribera, Avgda. Prat de la Riba 171, 08921, Santa Coloma de Gramenet, Spain

    Josep M. Campanera & F. Javier Luque

  2. Department of Physical Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Avgda. Diagonal 643, 08028, Barcelona, Spain

    Xavier Barril

  3. Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluís Companys 23, 08010, Barcelona, Spain

    Xavier Barril

Authors
  1. Josep M. Campanera
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier Barril
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Javier Luque
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Josep M. Campanera or F. Javier Luque.

Additional information

Published as part of the special collection of articles derived from the 8th Congress on Electronic Structure: Principles and Applications (ESPA 2012).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 279 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Campanera, J.M., Barril, X. & Luque, F.J. On the transferability of fractional contributions to the hydration free energy of amino acids. Theor Chem Acc 132, 1343 (2013). https://doi.org/10.1007/s00214-013-1343-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00214-013-1343-y

Keywords

Search

Navigation