What are the dielectric “constants” of proteins and how to validate electrostatic models?

Proteins: Structure, Function and Bioinformatics - Tập 44 Số 4 - Trang 400-417 - 2001
Claudia Schütz1, A. Warshel2
1Department of Chemistry, University of Southern California, Los Angeles, California USA
2Department of Chemistry University of Southern California Los Angeles, California

Tóm tắt

AbstractImplicit models for evaluation of electrostatic energies in proteins include dielectric constants that represent effect of the protein environment. Unfortunately, the results obtained by such models are very sensitive to the value used for the dielectric constant. Furthermore, the factors that determine the optimal value of these constants are far from being obvious. This review considers the meaning of the protein dielectric constants and the ways to determine their optimal values. It is pointed out that typical benchmarks for validation of electrostatic models cannot discriminate between consistent and inconsistent models. In particular, the observed pKa values of surface groups can be reproduced correctly by models with entirely incorrect physical features. Thus, we introduce a discriminative benchmark that only includes residues whose pKa values are shifted significantly from their values in water. We also use the semimacroscopic version of the protein dipole Langevin dipole (PDLD/S) formulation to generate a series of models that move gradually from microscopic to fully macroscopic models. These include the linear response version of the PDLD/S models, Poisson Boltzmann (PB)‐type models, and Tanford Kirkwwod (TK)‐type models. Using our different models and the discriminative benchmark, we show that the protein dielectric constant, εp, is not a universal constant but simply a parameter that depends on the model used. It is also shown in agreement with our previous works that εp represents the factors that are not considered explicitly. The use of a discriminative benchmark appears to help not only in identifying nonphysical models but also in analyzing effects that are not reproduced in an accurate way by consistent models. These include the effect of water penetration and the effect of the protein reorganization. Finally, we show that the optimal dielectric constant for self‐energies is not the optimal constant for charge‐charge interactions. Proteins 2001;44:400–417. © 2001 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1126/science.694508

10.1021/ar00069a004

10.1017/S0033583500005333

Warshel A, 1991, Computer modeling of chemical reactions in enzymes and solutions

10.1146/annurev.bb.19.060190.001505

10.1017/S0033583500005746

Matthew JB, 1985, Electrostatic effects in proteins, Annu Rev Biophys Biophys Chem, 14, 387, 10.1146/annurev.bb.14.060185.002131

10.1146/annurev.biochem.69.1.751

10.1016/0005-2728(90)90192-7

10.1021/jp9519070

10.1002/(SICI)1097-0134(19990901)36:4<484::AID-PROT13>3.0.CO;2-R

10.1146/annurev.bi.61.070192.004241

10.1016/S0006-3495(89)82662-1

10.1038/35009114

10.1093/protein/5.3.215

10.1021/jp9711499

10.1002/(SICI)1097-0134(19980301)30:4<407::AID-PROT8>3.0.CO;2-F

10.1021/bi000640e

10.1016/0022-2836(85)90411-5

10.1021/bi00374a006

10.1016/S0301-4622(96)02238-7

10.1002/prot.340150304

10.1002/prot.340200109

10.1006/jmbi.1994.1301

10.1016/S0006-3495(99)76868-2

10.1016/S0959-440X(98)80041-9

10.1021/ja960884f

10.1016/S0006-3495(98)77885-3

10.1016/S0006-3495(00)76411-3

10.1021/j100111a046

10.1016/S1380-7323(96)80049-5

10.1063/1.461760

10.1021/bi00355a035

10.1021/cr950045w

10.1002/(SICI)1096-987X(19961115)17:14<1587::AID-JCC1>3.0.CO;2-H

10.1016/0022-2836(88)90445-7

10.1021/bi00514a028

10.1021/jp963412w

10.1021/bi00496a010

10.1021/bi00435a001

10.1016/0022-2836(76)90311-9

10.1063/1.462997

10.1021/cr00023a004

10.1002/jcc.540140205

10.1063/1.477441

Warshel A, 1994, 72

10.1021/jp970882x

10.1063/1.475219

10.1063/1.1749489

10.1063/1.465468

10.1021/j100475a014

10.1063/1.456845

10.1063/1.445724

10.1063/1.466711

10.1021/j100084a049

10.1007/s007750050113

10.1073/pnas.81.15.4785

10.1021/ja01577a001

10.1021/bi00058a016

10.1073/pnas.88.13.5804

10.1021/bi00312a015

10.1021/jp962156k

10.1002/jcc.540130212

10.1021/ja00172a038

ChuZT VillàJ SchutzCN StrajblM WarshelA.2001. (In preparation)

Honig BH, 1983, Do “salt bridges” exist in membrane proteins, Biophys J, 41, 203

10.1002/pro.5560030206

10.1073/pnas.75.11.5250

10.1038/334270a0

10.1021/jp960111d

10.1146/annurev.bb.20.060191.001411

10.1016/S0969-2126(96)00052-4

10.1016/S0006-3495(91)82282-2

10.1021/j100665a011

10.1002/bip.360251106

10.1021/jp962478o

10.1021/jp973420s

10.1021/ja01685a008

10.1021/ja01421a013

10.1063/1.1723908

10.1002/(SICI)1097-0134(20000701)40:1<1::AID-PROT10>3.0.CO;2-O

10.1021/ja00154a031

10.1016/S0006-3495(97)78851-9

10.1021/ja00392a033

10.1021/bi970071j

10.1016/0022-2836(90)90313-B

10.1016/S0021-9258(19)42949-9

10.1016/0022-2836(90)90200-6

10.1016/0022-2836(91)80195-Z

10.1016/S0006-3495(94)80900-2

10.1016/0022-2836(74)90598-1

10.1002/prot.340150407

Doa‐pin S, 1991, Structural and thermodynamic consequences of buring a charged residue within the hydrophobic core of t4 lysozyme, Biochemistry, 30, 11521, 10.1021/bi00113a006

10.1021/bi00461a025

10.1111/j.1432-1033.1978.tb12546.x

10.1107/S0108767388000303

Fujii S, 1980, Acid denaturation steps of Streptomyces subtilisin inhibitor, J Biochem, 88, 789, 10.1093/oxfordjournals.jbchem.a133032

SuzukiT.Structural modulation of the protein proteinase inhibitor ssi (streptomyces subtilisin inhibitor). Forthcoming.

10.1021/bi991422s

10.1016/0022-2836(91)90215-R

Inagaki F, 1981, Nuclear magnetic resonance study on the microenvironments of histidine residues of ribonuclease t 1 and carboxymethylated ribonuclease t 1, J Biochem, 89, 1185

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Proteins: Structure, Function and Bioinformatics

Tập 44 Số 4

400-417

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