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Computational analyses of the surface properties of protein-protein interfaces.

Gruber J, Zawaira A, Saunders R, Barrett CP, Noble ME - Acta Crystallogr. D Biol. Crystallogr. (2006)

Bottom Line: Experiment remains the best way to answer this question, but computational tools can contribute where this fails.Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied.These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.

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Affiliation: Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, England.

ABSTRACT
Several potential applications of structural biology depend on discovering how one macromolecule might recognize a partner. Experiment remains the best way to answer this question, but computational tools can contribute where this fails. In such cases, structures may be studied to identify patches of exposed residues that have properties common to interaction surfaces and the locations of these patches can serve as the basis for further modelling or for further experimentation. To date, interaction surfaces have been proposed on the basis of unusual physical properties, unusual propensities for particular amino-acid types or an unusually high level of sequence conservation. Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied. These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.

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Distribution of hydrophobicity around tryptophan and arginine residues. The side chains of tryptophan (a, b) and arginine (c, d) are shown in either ball-and-stick (a, c) or molecular-surface (b, d) representation. Ball-and-stick representations are coloured by atom type, whereas the surface representation is coloured by GRID-assigned hydrophobic potential. Here, yellow indicates regions with high local hydrophobicity, while purple indicates nonhydrophobic surface patches.
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fig2: Distribution of hydrophobicity around tryptophan and arginine residues. The side chains of tryptophan (a, b) and arginine (c, d) are shown in either ball-and-stick (a, c) or molecular-surface (b, d) representation. Ball-and-stick representations are coloured by atom type, whereas the surface representation is coloured by GRID-assigned hydrophobic potential. Here, yellow indicates regions with high local hydrophobicity, while purple indicates nonhydrophobic surface patches.

Mentions: The GRID approach succeeds in predicting some aspects of protein-surface hydrophobicity that do not emerge from a simple categorization of underlying atoms. For example, while tryptophan is considered to be a hydrophobic amino acid, it does have the capacity to form polar interactions, particularly in the indole plane, through its N∊ atom (Fig. 2 ▶ a) and thus this part of the residue should properly be characterized as hydrophilic. The GRID analysis captures this intuitive behaviour (Fig. 2 ▶ b), clearly demonstrating hydrophilic patches on the surface resulting from the polar N∊ atom. Complementary intuitive behaviour is seen for arginine, a predominantly polar amino acid (Fig. 2 ▶ c). In addition to the generally hydrophilic periphery of the guanidino group, GRID’s hydrophobic probe identifies both the hydrophobic aliphatic part of the side chain and a partly hydrophobic surface that is parallel to the plane of the guanidino group (Fig. 2 ▶ d). This latter behaviour arises from the directional dependence of hydrogen bonds, which form preferentially in the plane of the guanidino moiety (Singh & Thornton, 1992 ▶).


Computational analyses of the surface properties of protein-protein interfaces.

Gruber J, Zawaira A, Saunders R, Barrett CP, Noble ME - Acta Crystallogr. D Biol. Crystallogr. (2006)

Distribution of hydrophobicity around tryptophan and arginine residues. The side chains of tryptophan (a, b) and arginine (c, d) are shown in either ball-and-stick (a, c) or molecular-surface (b, d) representation. Ball-and-stick representations are coloured by atom type, whereas the surface representation is coloured by GRID-assigned hydrophobic potential. Here, yellow indicates regions with high local hydrophobicity, while purple indicates nonhydrophobic surface patches.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483497&req=5

fig2: Distribution of hydrophobicity around tryptophan and arginine residues. The side chains of tryptophan (a, b) and arginine (c, d) are shown in either ball-and-stick (a, c) or molecular-surface (b, d) representation. Ball-and-stick representations are coloured by atom type, whereas the surface representation is coloured by GRID-assigned hydrophobic potential. Here, yellow indicates regions with high local hydrophobicity, while purple indicates nonhydrophobic surface patches.
Mentions: The GRID approach succeeds in predicting some aspects of protein-surface hydrophobicity that do not emerge from a simple categorization of underlying atoms. For example, while tryptophan is considered to be a hydrophobic amino acid, it does have the capacity to form polar interactions, particularly in the indole plane, through its N∊ atom (Fig. 2 ▶ a) and thus this part of the residue should properly be characterized as hydrophilic. The GRID analysis captures this intuitive behaviour (Fig. 2 ▶ b), clearly demonstrating hydrophilic patches on the surface resulting from the polar N∊ atom. Complementary intuitive behaviour is seen for arginine, a predominantly polar amino acid (Fig. 2 ▶ c). In addition to the generally hydrophilic periphery of the guanidino group, GRID’s hydrophobic probe identifies both the hydrophobic aliphatic part of the side chain and a partly hydrophobic surface that is parallel to the plane of the guanidino group (Fig. 2 ▶ d). This latter behaviour arises from the directional dependence of hydrogen bonds, which form preferentially in the plane of the guanidino moiety (Singh & Thornton, 1992 ▶).

Bottom Line: Experiment remains the best way to answer this question, but computational tools can contribute where this fails.Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied.These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Molecular Biophysics, Rex Richards Building, South Parks Road, Oxford OX1 3QU, England.

ABSTRACT
Several potential applications of structural biology depend on discovering how one macromolecule might recognize a partner. Experiment remains the best way to answer this question, but computational tools can contribute where this fails. In such cases, structures may be studied to identify patches of exposed residues that have properties common to interaction surfaces and the locations of these patches can serve as the basis for further modelling or for further experimentation. To date, interaction surfaces have been proposed on the basis of unusual physical properties, unusual propensities for particular amino-acid types or an unusually high level of sequence conservation. Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied. These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.

Show MeSH