For a series of different proteins, including a structural protein, enzyme, inhibitor, protein marker, and a charge-transfer system, we have quantified the higher affinity of Na+ over K+ to the protein surface by means of molecular dynamics simulations and conductivity measurements. Both approaches show that sodium binds at least twice as strongly to the protein surface than potassium does with this effect being present in all proteins under study. Different parts of the protein exterior are responsible to a varying degree for the higher surface affinity of sodium, with the charged carboxylic groups of aspartate and glutamate playing the most important role. Therefore, local ion pairing is the key to the surface preference of sodium over potassium, which is further demonstrated and quantified by simulations of glutamate and aspartate in the form of isolated amino acids as well as short oligopeptides. As a matter of fact, the effect is already present at the level of preferential pairing of the smallest carboxylate anions, formate or acetate, with Na+ versus K+, as shown by molecular dynamics and ab initio quantum chemical calculations. By quantifying and rationalizing the higher preference of sodium over potassium to protein surfaces, the present study opens a way to molecular understanding of many ion-specific (Hofmeister) phenomena involving protein interactions in salt solutions.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic and Center for Biomolecules and Complex Molecular Systems Flemingovo nám 2 16610 Prague 6 Czech Republic

Zobrazit více v PubMed

Nightingale ER. J Phys Chem. 1959;63:1381–1387.

Hofmeister F. Arch Exp Pathol Pharmakol (Leipzig) 1888;24:247–260.

Inouye K, Kuzuya K, Tonomura B. J Biochem (Tokyo) 1998;123:847–852. PubMed

Wolff J, Sackett DL, Knipling L. Protein Sci. 1996;5:2020–2028. PubMed PMC

Vogel HJ, Drakenberg T, Forsen S. In: NMR of Newly Accessible Nuclei. Laszlo P, editor. Vol 1. New York: Academic; 1983. pp. 157–197.

Darnell J, Lodish H, Baltimore D. Molecular Cell Biology. New York: Scientific American Books; 1990.

Gumbart J, Wang Y, Aksimentiev A, Tajkhorshid E, Schulten K. Curr Opin Struct Biol. 2005;15:423–431. PubMed PMC

Ash WL, Zlomislic MR, Oloo EO, Tieleman DP. Biochim Biophys Acta. 2004;1666:158–189. PubMed

Chen H, Wu Y, Voth GA. Biophys J. 2006;90:L73–L75. PubMed PMC

Allen TW, Andersen OS, Roux B. Biophys J. 2006;90:3447–3468. PubMed PMC

Collins KD. Biophys J. 1997;72:65–76. PubMed PMC

Marcus Y. Ion Solvation. Chichester, UK: Wiley; 1985.

Omta AW, Kropman MJ, Woutersen S, Bakker HJ. Science. 2003;301:347–349. PubMed

Collins KD. Methods. 2004;34:300–311. PubMed

Collins KD. Biophys Chem. 2006;119:271–281. PubMed

Siu FM, Ma NL, Tsang CW. Chem Eur J. 2004;10:1966–1976. PubMed

Arakawa T, Timasheff SN. Biochemistry. 1982;21:6545–6552. PubMed

Lin TY, Timasheff SN. Protein Sci. 1996;5:372–381. PubMed PMC

Weissenborn PK, Pugh RJ. J Colloid Interface Sci. 1996;184:550–563. PubMed

Vrbka L, Jungwirth P, Bauduin P, Touraud D, Kunz W. J Phys Chem B. 2006;110:7036–7043. PubMed

Robertson TB. J Biol Chem. 1911;9:303–326.

Maldonado S, Irun MP, Campos LA, Rubio JA, Luquita A, Lostao A, Wang RJ, Garcia-Moreno B, Sancho J. Protein Sci. 2002;11:1260–1273. PubMed PMC

Dominy BN, Perl D, Schmid FX, Brooks CL. J Mol Biol. 2002;319:541–554. PubMed

Muegge I, Schweins T, Warshel A. Proteins Struct Funct Bioinfo. 1998;30:407–423. PubMed

Curtis RA, Ulrich J, Montaser A, Prausnitz JM, Blanch HW. Biotechnol Bioeng. 2002;79:367–380. PubMed

Pinna MC, Bauduin P, Tourand D, Monduzzi M, Ninham BW, Kunz W. J Phys Chem B. 2005;109:16511–16514. PubMed

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindaylov IN, Bourne PE. Nucleic Acids Res. 2000;28:235–242. PubMed PMC

Berendsen HJC, Grigera JR, Straatsma TP. J Phys Chem. 1987;91:6269–6271.

Case DA, Darden TA, Cheatham TE III, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Wang B, Pearlman DA, et al. AMBER 8. San Francisco: Univ of California; 2004.

Wang JM, Cieplak P, Kollman PA. J Comput Chem. 2000;21:1049–1074.

Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG. J Chem Phys. 1995;103:8577–8593.

Ryckaert J-P, Ciccotti G, Berendsen HJC. J Comput Phys. 1977;23:327–341.

Dunning TH., Jr J Chem Phys. 1989;90:1007–1024.

Barone V, Cossi M. J Phys Chem A. 1998;102:1995–2001.

Cossi M, Rega N, Scalmani G, Barone V. J Comp Chem. 2003;24:669–681. PubMed

Schmid R, Miah AM, Sapunov VN. Phys Chem Chem Phys. 2000;2:97–102.

Anion-cation contrast of small molecule solvation in salt solutions

Beyond Hofmeister

Molecular model of a cell plasma membrane with an asymmetric multicomponent composition: water permeation and ion effects