DOI: 10.1110/ps.03486104. Energy functions for protein design I: Efficient and accurate continuum electrostatics and solvation

Energy functions for protein design I: Efficient and accurate continuum electrostatics and solvation

10.1110/ps.03486104

Crossref journal-article

Wiley

Protein Science (311)

Abstract

AbstractElectrostatics and solvation energies are important for defining protein stability, structural specificity, and molecular recognition. Because these energies are difficult to compute quickly and accurately, they are often ignored or modeled very crudely in computational protein design. To address this problem, we have developed a simple, fast, and accurate approximation for calculating Born radii in the context of protein design calculations. When these approximate Born radii are used with the generalized Born continuum dielectric model, energies calculated by the 106‐fold slower finite difference Poisson‐Boltzmann model are faithfully reproduced. A similar approach can be used for estimating solvent‐accessible surface areas (SASAs). As an independent test, we show that these approximations can be used to accurately predict the experimentally determined pKas of >200 ionizable groups from 15 proteins.

Bibliography

Pokala, N., & Handel, T. M. (2004). Energy functions for protein design I: Efficient and accurate continuum electrostatics and solvation. Protein Science, 13(4), 925â936. Portico.

Authors 2

Navin Pokala (first)
Tracy M. Handel (additional)

References 79 Referenced 75

10.1110/ps.33601
10.1006/jmbi.1994.1301
10.1021/bi9601565
10.1021/bi00496a010
10.1021/bi00093a013
10.1021/bi010427y
10.1002/pro.5560070122
10.1038/254304a0
10.1126/science.278.5335.82
10.1016/S0022-2836(03)00888-X
{'key': 'e_1_2_7_12_1', 'volume-title': 'Molecular biophysics: Structures in motion.', 'author': 'Daune M.', 'year': '1999'} / Molecular biophysics: Structures in motion. by Daune M. (1999)
10.1002/(SICI)1096-987X(200003)21:4<295::AID-JCC5>3.0.CO;2-8
10.1002/pro.5560041006
10.1021/jp984440c
10.1002/pro.5560060807
10.1021/jp962156k
10.1038/319199a0
10.1006/jmbi.2001.5009
10.1002/prot.10171
10.1093/protein/2.7.527
10.1002/prot.10174
10.1002/jcc.540090407
10.1038/nsb1296-1002
10.1038/nsb1296-1011
10.1063/1.1595641
10.1016/S0022-2836(02)00442-4
10.1073/pnas.96.20.11145
10.1038/nsb877
10.1016/0009-2614(95)01082-K
10.1002/pro.5560030206
10.1021/bi9605191
10.1021/j100108a002
10.1073/pnas.212068599
10.1021/ja9621760
10.1006/jmbi.1994.1366
10.1006/jmbi.1999.3211
10.1073/pnas.97.19.10383
10.1002/(SICI)1097-0134(19990501)35:2<133::AID-PROT1>3.0.CO;2-N
10.1002/jcc.540140309
10.1021/bi00132a025
10.1021/bi992271w
10.1038/nature01556
10.1021/bi00027a013
10.1038/nsb0698-470
10.1002/jcc.10104
10.1006/jmbi.2000.4319
10.1006/jmbi.2001.5326
10.1021/jp9537926
10.1016/S0959-440X(02)00345-7
10.1021/jp0267555
10.1038/89638
10.1021/bi00037a001
10.1002/jcc.540120405
10.1073/pnas.051624498
10.1021/bi981269m
10.1073/pnas.211436698
10.1021/jp994072s
10.1002/jcc.10126
10.1016/0092-8674(92)90145-3
10.1016/0960-9822(93)90063-T
10.1006/jsbi.2001.4349
10.1016/0022-2836(87)90358-5
{'key': 'e_1_2_7_64_1', 'volume-title': 'Numerical recipes in C: The art of scientific computing.', 'author': 'Press W.H.', 'year': '1999'} / Numerical recipes in C: The art of scientific computing. by Press W.H. (1999)
10.1021/jp961992r
10.1110/ps.9.6.1106
10.1021/jp9521621
10.1002/prot.1106
10.1073/pnas.92.2.452
10.1021/j100058a043
10.1021/bi992091m
10.1021/ja00172a038
10.1016/0022-2836(91)80195-Z
10.1016/S1359-0278(98)00036-4
10.1021/ja01577a001
10.1021/bi00761a029
10.1006/jmbi.2000.3758
10.1038/nsb0295-122
10.1002/prot.10332
10.1073/pnas.77.4.1736

Dates

Type	When
Created	21 years, 5 months ago (March 15, 2004, 8:13 p.m.)
Deposited	1 year, 10 months ago (Sept. 28, 2023, 2:01 p.m.)
Indexed	1 week, 2 days ago (Aug. 19, 2025, 6 a.m.)
Issued	21 years, 4 months ago (April 1, 2004)
Published	21 years, 4 months ago (April 1, 2004)
Published Online	16 years, 7 months ago (Jan. 1, 2009)
Published Print	21 years, 4 months ago (April 1, 2004)

Funders 0

None

BibTeX

@article{Pokala_2004, title={Energy functions for protein design I: Efficient and accurate continuum electrostatics and solvation}, volume={13}, ISSN={1469-896X}, url={http://dx.doi.org/10.1110/ps.03486104}, DOI={10.1110/ps.03486104}, number={4}, journal={Protein Science}, publisher={Wiley}, author={Pokala, Navin and Handel, Tracy M.}, year={2004}, month=apr, pages={925–936} }

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  "URL": "http://dx.doi.org/10.1110/ps.03486104",
  "relation": {},
  "ISSN": [
    "0961-8368",
    "1469-896X"
  ],
  "subject": [],
  "container-title-short": "Protein Science",
  "published": {
    "date-parts": [
      [
        2004,
        4
      ]
    ]
  }
}