Poisson-Boltzmann calculations of nonspecific salt effects on protein-protein binding free energies

被引:85
作者
Bertonati, Claudia
Honig, Barry
Alexov, Emil [1 ]
机构
[1] Columbia Univ, Howard Hughes Med Inst, Ctr Computat Biol & Bioinformat, New York, NY USA
[2] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA
关键词
D O I
10.1529/biophysj.106.092122
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The salt dependence of the binding free energy of five protein- protein hetero-dimers and two homo-dimers/tetramers was calculated from numerical solutions to the Poisson-Boltzmann equation. Overall, the agreement with experimental values is very good. In all cases except one involving the highly charged lactoglobulin homo-dimer, increasing the salt concentration is found both experimentally and theoretically to decrease the binding affinity. To clarify the source of salt effects, the salt-dependent free energy of binding is partitioned into screening terms and to self-energy terms that involve the interaction of the charge distribution of a monomer with its own ion atmosphere. In six of the seven complexes studied, screening makes the largest contribution but self-energy effects can also be significant. The calculated salt effects are found to be insensitive to force-field parameters and to the internal dielectric constant assigned to the monomers. Nonlinearities due to high charge densities, which are extremely important in the binding of proteins to negatively charged membrane surfaces and to nucleic acids, make much smaller contributions to the protein- protein complexes studied here, with the exception of highly charged lactoglobulin dimers. Our results indicate that the Poisson-Boltzmann equation captures much of the physical basis of the nonspecific salt dependence of protein- protein complexation.
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收藏
页码:1891 / 1899
页数:9
相关论文
共 60 条
[1]   Biophysical characterization of the interaction of the β-lactamase TEM-1 with its protein inhibitor BLIP [J].
Albeck, S ;
Schreiber, G .
BIOCHEMISTRY, 1999, 38 (01) :11-21
[3]   Incorporating protein conformational flexibility into the calculation of pH-dependent protein properties [J].
Alexov, EG ;
Gunner, MR .
BIOPHYSICAL JOURNAL, 1997, 72 (05) :2075-2093
[4]  
Baker N, 2000, J COMPUT CHEM, V21, P1343, DOI 10.1002/1096-987X(20001130)21:15<1343::AID-JCC2>3.0.CO
[5]  
2-K
[6]  
BASHFORD D, 1997, OBJECT ORIENTED PROG
[7]   Electrostatic binding of proteins to membranes. Theoretical predictions and experimental results with charybdotoxin and phospholipid vesicles [J].
BenTal, N ;
Honig, B ;
Miller, C ;
McLaughlin, S .
BIOPHYSICAL JOURNAL, 1997, 73 (04) :1717-1727
[8]   Binding of small basic peptides to membranes containing acidic lipids: Theoretical models and experimental results [J].
BenTal, N ;
Honig, B ;
Peitzsch, RM ;
Denisov, G ;
McLaughlin, S .
BIOPHYSICAL JOURNAL, 1996, 71 (02) :561-575
[9]   BIOPHYSICAL STUDY OF HALOPHILIC MALATE-DEHYDROGENASE IN SOLUTION - REVISED SUBUNIT STRUCTURE AND SOLVENT INTERACTIONS OF NATIVE AND RECOMBINANT ENZYME [J].
BONNETE, F ;
EBEL, C ;
ZACCAI, G ;
EISENBERG, H .
JOURNAL OF THE CHEMICAL SOCIETY-FARADAY TRANSACTIONS, 1993, 89 (15) :2659-2666
[10]   Fast boundary element method for the linear Poisson-Boltzmann equation [J].
Boschitsch, AH ;
Fenley, MO ;
Zhou, HX .
JOURNAL OF PHYSICAL CHEMISTRY B, 2002, 106 (10) :2741-2754