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. 2011 Jan;39(1):30-43.
doi: 10.1093/nar/gkq736. Epub 2010 Sep 2.

M-ORBIS: mapping of molecular binding sites and surfaces

Laurent-Philippe Albou  1 , Olivier Poch, Dino Moras
Affiliations

M-ORBIS: mapping of molecular binding sites and surfaces

Laurent-Philippe Albou et al. Nucleic Acids Res. 2011 Jan.

Abstract

M-ORBIS is a Molecular Cartography approach that performs integrative high-throughput analysis of structural data to localize all types of binding sites and associated partners by homology and to characterize their properties and behaviors in a systemic way. The robustness of our binding site inferences was compared to four curated datasets corresponding to protein heterodimers and homodimers and protein-DNA/RNA assemblies. The Molecular Cartographies of structurally well-detailed proteins shows that 44% of their surfaces interact with non-solvent partners. Residue contact frequencies with water suggest that ∼86% of their surfaces are transiently solvated, whereas only 15% are specifically solvated. Our analysis also reveals the existence of two major binding site families: specific binding sites which can only bind one type of molecule (protein, DNA, RNA, etc.) and polyvalent binding sites that can bind several distinct types of molecule. Specific homodimer binding sites are for instance nearly twice as hydrophobic than previously described and more closely resemble the protein core, while polyvalent binding sites able to form homo and heterodimers more closely resemble the surfaces involved in crystal packing. Similarly, the regions able to bind DNA and to alternatively form homodimers, are more hydrophobic and less polar than previously described DNA binding sites.

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Figures

Figure 1.
Figure 1.
The M-ORBIS matrix as a specialized multiple alignment of structures. The M-ORBIS output matrix is obtained via a 7-step workflow illustrated in the left part of the figure. As in traditional multiple alignments of sequences or structures, the M-ORBIS matrix gives access to every homologous chain and residue. Nevertheless, to perform the complex task of Molecular Cartography, M-ORBIS also stores information relative to the residue locations (field I.), to the physico-chemical and geometrical properties (field II.) and to the interacting state (field III.) of each analyzed residue. A cell of the M-ORBIS matrix is illustated in the right-hand table and gives insights into some of the properties that are stored. For instance, field III.c indicates that the first residue is involved in only homodimeric interaction in two of six related structural chains. A polyvalent binding site is detected when for a given residue (column), the corresponding residues of related structural chains are involved in at least two different binding site types (residue described in column 5). A specific binding site is inferred when only one binding site type is detected at that position (residue described in column 1).
Figure 2.
Figure 2.
Protein–water contacts at different contact frequencies. (A, B, C and D) Structures of the guanine nucleotide-binding protein G(i) (PDB: 1BOF), while (E), (F), (G) and (H) are structures of the H1N1 Neuraminidase (PDB: 3b7e). In (A) and (E), the contact frequencies fcontact with water molecules are shown, as calculated by M-ORBIS with 49 and 169 related chains, respectively; non-solvated regions are indicated in dark blue (fcontact ∼0%), while partially solvated regions are in green (fcontact ∼50%). Red surfaces correspond to the regions that specifically bind water molecules with a fcontact ∼100%. The surface in contact with water molecules is shown in light blue in (B), (C), (D), (F), (G), (H) with fcontact of 25, 50, 75, 50, 75 and 90%, respectively. For these two molecules, the central solvated regions are ligand binding sites.
Figure 3.
Figure 3.
Examples of proteins exhibiting polyvalent binding sites. Polyvalent binding sites are a general phenomena in molecular structures. (A) The TATA-binding protein (TBP) processed by the M-ORBIS Molecular Cartography approach starting from structure 1ais:A. (B) The Retinoid X Receptor-Alpha (RXR) cartography from the structure 1dkf:A. (C) The Pancreatic Alpha-Amylase (PAA) cartography from the structure 1dhk:A. Binding site types are represented in different colors: blue for homodimer, red for heterodimer, yellow for DNA, green for ligand and salmon for peptide. For TBP and RXR, the homodimer partner shown is extracted from structures 1d3u and 1dkf, respectively. For PAA, the heterodimeric and peptide partners are extracted from structures 1dhk and 1clv, respectively, whereas the ligand partner was extracted from 1g9h.
Figure 4.
Figure 4.
Change of conformation between molecular contexts: the case of CDK. Molecular Cartography obtained from the structure of the CDK2 (1fin:A). Two molecular contexts are defined: MC1 corresponds to the CDK2 in an environment where it interacts with water and ligand only, whereas MC2 corresponds to an environment where it also interacts with another protein to form a heterodimer. For each of these molecular contexts, the corresponding sets of structures has been automatically detected by M-ORBIS and an averaged backbone is computed and shown in (A and B). Two main conformational changes are involved between MC1 and MC2: the T-Coil helix moves towards the heterodimer binding site, while the PSTAIRE-helix is pushed in the opposite direction. The amount of conformational change has been mapped onto the protein surface in (C); blue, no change; green, small change; red, important change. The molecular cartography shown in (D) allows to correlate these conformational changes with the location of each binding site type.
Figure 5.
Figure 5.
Molecular Cartography of binding sites. Heterodimeric binding sites are represented in red, homodimeric and ligand binding sites in blue and green, respectively and DNA and peptide binding sites in yellow and salmon, respectively. Polyvalent binding sites are indicated in purple. From top left to bottom right, the cartography of proteins: ribonuclease inhibitor (1dfj), ferrodoxin-nadp reductase (1ewy); neuraminidase (3b7e); cAMP-dependent kinase (1ydr); p53 tumor suppressor (1tsr); neurotoxin bont/A (1xtg); acetylcholinesterase (1fss); guanine nucleotide-binding protein G(i) (1bof).
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References

    1. Bartlett GJ, Todd AE, Thornton JM. Inferring protein function from structure. Methods Biochem. Anal. 2003;44:387–407. - PubMed
    1. Brylinski M, Kochanczyk M, Broniatowska E, Roterman I. Localization of ligand binding site in proteins identified in silico. J. Mol. Model. 2007;13:665–675. - PubMed
    1. Porollo A, Meller J. Prediction-based fingerprints of protein-protein interactions. Proteins. 2007;66:630–645. - PubMed
    1. Jones S, Thornton JM. Searching for functional sites in protein structures. Curr. Opin. Chem. Biol. 2004;8:3–7. - PubMed
    1. Domingues FS, Rahnenfuhrer J, Lengauer T. Conformational analysis of alternative protein structures. Bioinformatics. 2007;23:3131–3138. - PubMed

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