DOI: 10.1002/prot.340050407. Molecular dynamics effects on protein electrostatics

Molecular dynamics effects on protein electrostatics

10.1002/prot.340050407

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractElectrostatic calculations have been carried out on a number of structural conformers of tuna cytochrome c Conformers were generated using molecular dynamics simulations with a range of solvent simulating, macroscopic dielectric formalisms, and one solvent model that explicitly included solvent water molecules. Structures generated using the lowest dielectric models were relatively tight, with‐side chains collapsed on the surface, while those from the higher dielectric modelshad more internal and external fluidity, with surface side chains exploring a fuller range of conformational space. The average structure generated with the explicitly solvated model corresponded most closely with the crystal structure. Individual pK values, overall titration curves, and electrostatic potential surfaces were calculated for average structures and along each simulation. Differences between structural conformers within each simulation give rise to substantial changes in calculated local electrostatic interactions, resulting in pK value fluctuations for individual sites in the protein that very by 0.3–2.0 pK units from the calculated time average. These variations are due to the thermal side chain reorientations that produce fluctuations in charge site separations. Properties like overall titration curves and pH dependent stability are not as sensitive to side chain fluctuations within a simulation, but there are substantial effects between simulation due to markeddifferences in average side chain behavior. These findings underscore the importance of proper dielectric formalism in molecular dynamics simulations when used to generate alternate solution structures from a crystal structure, and suggest that conformers significantly removed from the averagestructure have altered electrostatic properties that may prove important inepisodic protein properties such as catalysis.

Bibliography

Wendoloski, J. J., & Matthew, J. B. (1989). Molecular dynamics effects on protein electrostatics. Proteins: Structure, Function, and Bioinformatics, 5(4), 313â321. Portico.

Authors 2

John J. Wendoloski (first)
James B. Matthew (additional)

References 29 Referenced 48

10.1016/0076-6879(86)30019-3
10.1146/annurev.bb.14.060185.002131 / Annu. Rev. Biophys. Biophys. Chem. / Electrostatic effects in proteins by Matthew J. B. (1985)
10.1021/bi00263a024
10.1038/301169a0
10.1016/S0021-9258(18)89060-3 / J. Biol. Chem. / Electrostatic interactions during electron transfer reaction between c‐type cytochromes and flavodoxin by Weber P. C. (1985)
10.1021/bi00370a049
10.1016/0022-2836(82)90505-8
10.1038/330084a0
10.1002/prot.340030104
10.1002/jcc.540090407
10.1126/science.2823387
{'key': 'e_1_2_1_13_2', 'first-page': '113', 'article-title': 'Time dependent fluctuation of tuna cytochrome c: Effect of dielectric function', 'volume': '53', 'author': 'Wendoloski J. J.', 'year': '1988', 'journal-title': 'Biophys. J.'} / Biophys. J. / Time dependent fluctuation of tuna cytochrome c: Effect of dielectric function by Wendoloski J. J. (1988)
10.1016/0022-2836(81)90528-3
10.1016/0022-2836(81)90529-5
10.1016/S0022-2836(77)80200-3
10.1002/jcc.540020311
10.1021/ja00315a051
10.1021/bk-1987-0353.ch008
10.1063/1.445869
10.1016/0022-2836(71)90324-X
10.1016/0006-291X(78)91549-8
10.1073/pnas.83.10.3267
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10.1146/annurev.bi.46.070177.001503
{'key': 'e_1_2_1_27_2', 'first-page': '5197', 'article-title': 'Protein NMR Studies of histidine‐ionizations in myoglobins of various species', 'volume': '17', 'author': 'Botelho L. H.', 'year': '1978', 'journal-title': 'Comparison of observed and computed pK values. Biochemistry'} / Comparison of observed and computed pK values. Biochemistry / Protein NMR Studies of histidine‐ionizations in myoglobins of various species by Botelho L. H. (1978)
10.1126/science.2838904
10.1016/S0021-9258(18)88903-7 / J. Biol. Chem. / Electrostatic deformation of DNA by a DNA‐binding protein by Matthew J. B. (1985)
10.1101/SQB.1983.047.01.049

Dates

Type	When
Created	20 years, 2 months ago (May 28, 2005, 9:02 p.m.)
Deposited	1 year, 10 months ago (Oct. 22, 2023, 3:22 p.m.)
Indexed	1 year, 9 months ago (Oct. 31, 2023, 4 p.m.)
Issued	36 years, 7 months ago (Jan. 1, 1989)
Published	36 years, 7 months ago (Jan. 1, 1989)
Published Online	21 years, 6 months ago (Feb. 3, 2004)
Published Print	36 years, 7 months ago (Jan. 1, 1989)

Funders 0

None

BibTeX

@article{Wendoloski_1989, title={Molecular dynamics effects on protein electrostatics}, volume={5}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.340050407}, DOI={10.1002/prot.340050407}, number={4}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Wendoloski, John J. and Matthew, James B.}, year={1989}, month=jan, pages={313–321} }

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