Experimental measurement of the effective dielectric in the hydrophobic core of a protein

García-Moreno, Bertrand; Dwyer, John J.; Gittis, Apostolos G.; Lattman, Eaton E.; Spencer, Daniel S.; Stites, Wesley E.

doi:10.1016/s0301-4622(96)02238-7

Cited by 242 publications

(287 citation statements)

References 57 publications

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“…In calculating the excitonic interaction coefficients, the choice of the dielectric constant value, and the method chosen for screening and local field effects is no trivial matter [28]. Typically, effective protein dielectric constant values are chosen between 2 and 4; however, experimental measures of the dielectric coefficients in protein hydrophobic pockets indicate this value is well above this range, arguing against this practice [29]. The experimentally measured tubulin optical dielectric value of 8.41 falls well outside this range [30], and is expected to have a significant impact on coupling strengths.…”

Section: Resultsmentioning

confidence: 99%

The feasibility of coherent energy transfer in microtubules

Craddock

Friesen

Mane

et al. 2014

J. R. Soc. Interface.

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It was once purported that biological systems were far too 'warm and wet' to support quantum phenomena mainly owing to thermal effects disrupting quantum coherence. However, recent experimental results and theoretical analyses have shown that thermal energy may assist, rather than disrupt, quantum coherent transport, especially in the 'dry' hydrophobic interiors of biomolecules. Specifically, evidence has been accumulating for the necessary involvement of quantum coherent energy transfer between uniquely arranged chromophores in light harvesting photosynthetic complexes. The 'tubulin' subunit proteins, which comprise microtubules, also possess a distinct architecture of chromophores, namely aromatic amino acids, including tryptophan. The geometry and dipolar properties of these aromatics are similar to those found in photosynthetic units indicating that tubulin may support coherent energy transfer. Tubulin aggregated into microtubule geometric lattices may support such energy transfer, which could be important for biological signalling and communication essential to living processes. Here, we perform a computational investigation of energy transfer between chromophoric amino acids in tubulin via dipole excitations coupled to the surrounding thermal environment. We present the spatial structure and energetic properties of the tryptophan residues in the microtubule constituent protein tubulin. Plausibility arguments for the conditions favouring a quantum mechanism of signal propagation along a microtubule are provided. Overall, we find that coherent energy transfer in tubulin and microtubules is biologically feasible.

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Section: Resultsmentioning

confidence: 99%

The feasibility of coherent energy transfer in microtubules

Craddock

Friesen

Mane

et al. 2014

J. R. Soc. Interface.

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“…X-ray crystallography and equilibrium thermodynamic studies were used previously to characterize in detail the properties of internal Glu and Lys residues at positions 66 and 92 in staphylococcal nuclease (SNase) (11)(12)(13)(22)(23)(24). The crystal structures show that these internal groups are buried deeply in the hydrophobic core of the protein.…”

Section: Resultsmentioning

confidence: 99%

High tolerance for ionizable residues in the hydrophobic interior of proteins

Isom

Cannon

Castañeda

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

129

193

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Internal ionizable groups are quite rare in water-soluble globular proteins. Presumably, this reflects the incompatibility between charges and the hydrophobic environment in the protein interior. Here we show that proteins can have an inherently high tolerance for internal ionizable groups. The 25 internal positions in staphylococcal nuclease were substituted one at a time with Lys, Glu, or Asp without abolishing enzymatic activity and without detectable changes in the conformation of the protein. Similar results with substitutions of 6 randomly chosen internal positions in ribonuclease H with Lys and Glu suggest that the ability of proteins to tolerate internal ionizable groups might be a property common to many proteins. Eighty-six of the 87 substitutions made were destabilizing, but in all but one case the proteins remained in the native state at neutral pH. By comparing the stability of each variant protein at two different pH values it was established that the pKa values of most of the internal ionizable groups are shifted; many of the internal ionizable groups are probably neutral at physiological pH values. These studies demonstrate that special structural adaptations are not needed for ionizable groups to exist stably in the hydrophobic interior of proteins. The studies suggest that enzymes and other proteins that use internal ionizable groups for functional purposes could have evolved through the random accumulation of mutations that introduced ionizable groups at internal positions, followed by evolutionary adaptation and optimization to modulate stability, dynamics, and other factors necessary for function.electrostatics ͉ internal ionizable groups ͉ pKa values ͉ dehydration

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“…One way to fix this is to invoke a stronger dielectric screening (a much larger dielectric constant) in the Coulomb interaction between charged residues as suggested by Warshel and coworkers in another context (32). There is some experimental evidence for this (28). Another possible approach to fix this problem is to introduce a penalty function between oppositely charged residues as was suggested by Jacobson and Friesner in connection with their loop geometry optimizations (unpublished results).…”

Section: Resultsmentioning

confidence: 99%

Can a continuum solvent model reproduce the free energy landscape of a β-hairpin folding in water?

Zhou

Berne²

2002

Proc. Natl. Acad. Sci. U.S.A.

340

314

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The folding free energy landscape of the C-terminal ␤-hairpin of protein G is explored using the surface-generalized Born (SGB) implicit solvent model, and the results are compared with the landscape from an earlier study with explicit solvent model. The OPLSAA force field is used for the ␤-hairpin in both implicit and explicit solvent simulations, and the conformational space sampling is carried out with a highly parallel replica-exchange method. Surprisingly, we find from exhaustive conformation space sampling that the free energy landscape from the implicit solvent model is quite different from that of the explicit solvent model. In the implicit solvent model some nonnative states are heavily overweighted, and more importantly, the lowest free energy state is no longer the native ␤-strand structure. An overly strong saltbridge effect between charged residues (E42, D46, D47, E56, and K50) is found to be responsible for this behavior in the implicit solvent model. Despite this, we find that the OPLSAA͞SGB energies of all the nonnative structures are higher than that of the native structure; thus the OPLSAA͞SGB energy is still a good scoring function for structure prediction for this ␤-hairpin. Furthermore, the ␤-hairpin population at 282 K is found to be less than 40% from the implicit solvent model, which is much smaller than the 72% from the explicit solvent model and Ϸ80% from experiment. On the other hand, both implicit and explicit solvent simulations with the OPLSAA force field exhibit no meaningful helical content during the folding process, which is in contrast to some very recent studies using other force fields.P rotein-folding and -unfolding studies are of great current interest in molecular biology (1, 2). Experiments that probe proteins at different stages of the folding process have helped to elucidate kinetic mechanisms and the thermodynamic stabilities of folding (3-6). However, many of the details of protein-folding pathways remain unknown. Computer simulations performed at various levels of complexity ranging from simple lattice models, models with implicit solvent, to all-atom models with explicit solvent can be used to supplement experiment and fill in some of the gaps in our knowledge about folding pathways. Because explicit solvent simulations require enormous amounts of CPU time, many recent studies have been carried out with implicit solvent models (7-10). However, it is still an open question as to how well these implicit solvent models can predict the thermodynamics as well as the kinetics of protein folding. It will be very interesting to determine whether implicit solvent models can reproduce either the results from explicit solvent simulations or experimental results.The C terminus ␤-hairpin of protein G has received much attention recently on both the experimental and theoretical fronts (3-6, 11-16), because it is believed to be one of the smallest naturally occurring systems that exhibit many features of a full-size protein and also because it is a fast folder (folds in Ϸ6 s). Und...

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Experimental measurement of the effective dielectric in the hydrophobic core of a protein

Cited by 242 publications

References 57 publications

The feasibility of coherent energy transfer in microtubules

The feasibility of coherent energy transfer in microtubules

High tolerance for ionizable residues in the hydrophobic interior of proteins

Can a continuum solvent model reproduce the free energy landscape of a β-hairpin folding in water?

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