Solvent accessible surface area approximations for rapid and accurate protein structure prediction

Durham, Elizabeth; Dorr, Brent; Woetzel, Nils; Staritzbichler, René; Meiler, Jens

doi:10.1007/s00894-009-0454-9

Cited by 294 publications

(174 citation statements)

References 54 publications

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“…Considerable effort has been devoted to the search for a general scale that might relate the physical properties of the side-chain of each the 20 amino acids to its solvent-accessible surface area in folded proteins (ASA fold ), as determined using a probe that is often a water-sized sphere (24)(25)(26)(27)(28)(29)(30)(31)(32). Values of ASA fold depend on the size and shape of the probe, the presence or absence of steric constraints on the approach of a probe that may be imposed by flanking peptide bonds, and the rotameric preferences of the larger side-chains, all of which can affect the normalization of estimated ASA values.…”

Section: Relationship Between Side-chain Transfer Equilibria and Proteinmentioning

confidence: 99%

Temperature dependence of amino acid hydrophobicities

Wolfenden

Lewis

Yuan

et al. 2015

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

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The hydrophobicities of the 20 common amino acids are reflected in their tendencies to appear in interior positions in globular proteins and in deeply buried positions of membrane proteins. To determine whether these relationships might also have been valid in the warm surroundings where life may have originated, we examined the effect of temperature on the hydrophobicities of the amino acids as measured by the equilibrium constants for transfer of their side-chains from neutral solution to cyclohexane (K w>c ). The hydrophobicities of most amino acids were found to increase with increasing temperature. Because that effect is more pronounced for the more polar amino acids, the numerical range of K w>c values decreases with increasing temperature. There are also modest changes in the ordering of the more polar amino acids. However, those changes are such that they would have tended to minimize the otherwise disruptive effects of a changing thermal environment on the evolution of protein structure. Earlier, the genetic code was found to be organized in such a way that-with a single exception (threonine)-the side-chain dichotomy polar/ nonpolar matches the nucleic acid base dichotomy purine/pyrimidine at the second position of each coding triplet at 25°C. That dichotomy is preserved at 100°C. The accessible surface areas of amino acid side-chains in folded proteins are moderately correlated with hydrophobicity, but when free energies of vapor-tocyclohexane transfer (corresponding to size) are taken into consideration, a closer relationship becomes apparent.T he equilibrium conformations of proteins in neutral solution are strongly influenced by interactions between their constituent amino acids and solvent water. Early work on the crystal structure of hemoglobin and related proteins showed that the side-chains of the more polar amino acid residues tend to be exposed to solvent, whereas less polar side-chains tend to be buried within the interior of globular proteins (1). Later, those tendencies were put to a quantitative test by measuring equilibria of transfer of amino acid side-chains from neutral aqueous solution into less polar environments, such as the vapor phase (2, 3) or a nonpolar solvent such as cyclohexane (4), which dissolves only ∼2 × 10 −3 M water at saturation (5) and appears to be devoid of specific interactions with solutes. The water-to-cyclohexane distribution coefficients (K w>c ) of the 20 common sidechains [here termed "hydrophobicities" (6, 7) and expressed in concentration units of mol/L in each phase; SI Appendix] were found to span a range of 15 orders of magnitude at pH 7 and 25°C. Values of K w>c have been shown to be related to their outside-to-inside distributions in globular proteins (4,8) and to their tendencies to appear within the buried sequences of transmembrane proteins (9-11).Those solvent distribution experiments were conducted at what we would consider ordinary temperatures. However, there is widespread (12, 13)-if not universal (14)-agreement that life originated when the ea...

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Section: Relationship Between Side-chain Transfer Equilibria and Proteinmentioning

confidence: 99%

Temperature dependence of amino acid hydrophobicities

Wolfenden

Lewis

Yuan

et al. 2015

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

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“…In contrast to the reasonable (negative) correlation (r 2 = 0.83) of the normalized retention times with overall hydrophobicity as represented by log D, no significant correlations with retention were obtained with either the solvent-accessible surface areas of the amino acids [41] or the partial molar volumes of the amino acid side chains [42], the data for which were obtained in the cited references.…”

Section: Retention Behaviour and Correlationsmentioning

confidence: 71%

Direct determination of amino acids by hydrophilic interaction liquid chromatography with charged aerosol detection

Socia

Foley

2016

Journal of Chromatography A

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“…Ligands exposed to the surface area are uniquely dependent on interactions with the solvent and protein core. These parameters are assessed by SASA (Solvent accessible surface area) [33] . In LRP6, free energy of salvation ranged from 620 to 740 nm 2 ( fig.…”

Section: Ligandmentioning

confidence: 99%

Role of Hydrophobic Patch in LRP6: A Promising Drug Target for Alzheimer's disease

Muthusamy¹,

Prasad²

2016

ijps

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Muthusamy, et al.: Hydrophobic Patch in LRP6 for Alzheimer's disease Alzheimer's disease is one of the most fatal dementia occurring in elderly persons. LRP6 and DKK1 proteins are found in the senile plaques of Alzheimer's disease patients. Inducing the disassociation/inhibition of the LRP6-DKK1 complex is a vital mechanism for the treatment of Alzheimer's disease. This study accomplished its goal of targeting potent inhibitors against LRP6 by molecular modeling techniques such as high throughput virtual screening and molecular dynamics simulations. Zinc database compounds were docked in the hydrophobic patch of LRP6 and in the active site of DKK1 using the GLIDE module. The initial docking results were well exemplified to amino acid residues interacting on the hydrophobic patch of LRP6 and active sites of DKK1. Further, the best hit compounds (866) were again redocked with Glide XP and finally six lead compounds were identified as the best inhibitors against LRP6 which was later confirmed by molecular dynamics simulation studies.

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Solvent accessible surface area approximations for rapid and accurate protein structure prediction

Cited by 294 publications

References 54 publications

Temperature dependence of amino acid hydrophobicities

Temperature dependence of amino acid hydrophobicities

Direct determination of amino acids by hydrophilic interaction liquid chromatography with charged aerosol detection

Role of Hydrophobic Patch in LRP6: A Promising Drug Target for Alzheimer's disease

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