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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.

Show MeSH
The SH3 domain of Abl tyrosine kinase (PDB code 1abo) complex surface properties and function. (a) The secondary-structure representation of the Abl tyrosine kinase, showing a typical SH3 domain. (b) A molecular-surface representation including the proline-rich ligand peptide as a ball-and-stick model. The surface is coloured by local surface hydrophobicity, with strongly hydrophobic surfaces coloured yellow and weakly hydrophobic surfaces elements coloured green.
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fig3: The SH3 domain of Abl tyrosine kinase (PDB code 1abo) complex surface properties and function. (a) The secondary-structure representation of the Abl tyrosine kinase, showing a typical SH3 domain. (b) A molecular-surface representation including the proline-rich ligand peptide as a ball-and-stick model. The surface is coloured by local surface hydrophobicity, with strongly hydrophobic surfaces coloured yellow and weakly hydrophobic surfaces elements coloured green.

Mentions: An example of the insight that can be gained from the GRID-type hydrophobic analysis is illustrated in Fig. 3 ▶. SH3 domains generally bind a proline-rich peptide motif. From an analysis of the fold of an isolated SH3 domain (Fig. 3 ▶ a), relatively few insights into the peptide-binding mechanism could be derived (Musacchio et al., 1992 ▶). However, the hydrophobic surface potential reveals a striking correlation between the binding pattern of the naturally occurring ligand, as seen in the crystal structure of an SH3–peptide complex (Musacchio et al., 1994 ▶), and the local surface hydrophobicity (Fig. 3 ▶ b).


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)

The SH3 domain of Abl tyrosine kinase (PDB code 1abo) complex surface properties and function. (a) The secondary-structure representation of the Abl tyrosine kinase, showing a typical SH3 domain. (b) A molecular-surface representation including the proline-rich ligand peptide as a ball-and-stick model. The surface is coloured by local surface hydrophobicity, with strongly hydrophobic surfaces coloured yellow and weakly hydrophobic surfaces elements coloured green.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: The SH3 domain of Abl tyrosine kinase (PDB code 1abo) complex surface properties and function. (a) The secondary-structure representation of the Abl tyrosine kinase, showing a typical SH3 domain. (b) A molecular-surface representation including the proline-rich ligand peptide as a ball-and-stick model. The surface is coloured by local surface hydrophobicity, with strongly hydrophobic surfaces coloured yellow and weakly hydrophobic surfaces elements coloured green.
Mentions: An example of the insight that can be gained from the GRID-type hydrophobic analysis is illustrated in Fig. 3 ▶. SH3 domains generally bind a proline-rich peptide motif. From an analysis of the fold of an isolated SH3 domain (Fig. 3 ▶ a), relatively few insights into the peptide-binding mechanism could be derived (Musacchio et al., 1992 ▶). However, the hydrophobic surface potential reveals a striking correlation between the binding pattern of the naturally occurring ligand, as seen in the crystal structure of an SH3–peptide complex (Musacchio et al., 1994 ▶), and the local surface hydrophobicity (Fig. 3 ▶ b).

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