Limits...
Optimal ligand descriptor for pocket recognition based on the Beta-shape.

Kim JK, Won CI, Cha J, Lee K, Kim DS - PLoS ONE (2015)

Bottom Line: Pocket recognition and definition is frequently a prerequisite of structure-based virtual screening, reducing the search space of the predicted protein-ligand complex.In this paper, we present an optimal ligand shape descriptor for a pocket recognition algorithm based on the beta-shape, which is a derivative structure of the Voronoi diagram of atoms.The performance of the proposed algorithm is verified by a benchmark test.

View Article: PubMed Central - PubMed

Affiliation: Voronoi Diagram Research Center, Hanyang University, Seoul, Korea.

ABSTRACT
Structure-based virtual screening is one of the most important and common computational methods for the identification of predicted hit at the beginning of drug discovery. Pocket recognition and definition is frequently a prerequisite of structure-based virtual screening, reducing the search space of the predicted protein-ligand complex. In this paper, we present an optimal ligand shape descriptor for a pocket recognition algorithm based on the beta-shape, which is a derivative structure of the Voronoi diagram of atoms. We investigate six candidates for a shape descriptor for a ligand using statistical analysis: the minimum enclosing sphere, three measures from the principal component analysis of atoms, the van der Waals volume, and the beta-shape volume. Among them, the van der Waals volume of a ligand is the optimal shape descriptor for pocket recognition and best tunes the pocket recognition algorithm based on the beta-shape for efficient virtual screening. The performance of the proposed algorithm is verified by a benchmark test.

No MeSH data available.


A schematic diagram of a molecule and its beta-shape. Figure drawn by using the BetaConcept[44] and BetaMol program freely available from VDRC.(a) A two-dimensional molecule, (b) A two-dimensional molecule and its Connolly surface corresponding to the red circular probe, and (c) the beta-shape corresponding to the probe, (d) the van der Waals model of a protein (PDB id 1oq5), (e) the Connolly surface for water molecule (with 1.4Å radius), and (f) the corresponding beta-shape.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4383629&req=5

pone.0122787.g001: A schematic diagram of a molecule and its beta-shape. Figure drawn by using the BetaConcept[44] and BetaMol program freely available from VDRC.(a) A two-dimensional molecule, (b) A two-dimensional molecule and its Connolly surface corresponding to the red circular probe, and (c) the beta-shape corresponding to the probe, (d) the van der Waals model of a protein (PDB id 1oq5), (e) the Connolly surface for water molecule (with 1.4Å radius), and (f) the corresponding beta-shape.

Mentions: For the proximity among the atoms on the molecular boundary, the concept of the beta-shape has been proposed [37]. Fig. 1(a) shows a two-dimensional molecule. Fig. 1(b) shows the Connolly surface (green curve) corresponding to the red circular probe where the radius is β. Suppose that the Connolly surface is straightened by substituting the straight edges for the circular arcs and the planar triangles for the spherical triangles where their vertices are the centers of the related atoms. The straightened object bounded by the planar facets is the beta-shape of the molecule. Fig. 1(c) shows the beta-shape of a molecule corresponding to the red circular probe in Fig. 1(b). The beta-shape concisely provides the precise proximity among the atoms on the molecular boundary with respect to the probe. Fig. 1(d), (e), and (f) show the van der Waals model of a protein (PDB id 1oq5), its Connolly surface for water molecule with 1.4Å radius, and the corresponding beta-shape. We note here that the beta-shape is efficiently computed from the quasi triangulation which is the dual structure of the Voronoi diagram of atoms. The details are reported in [37, 41–43] and readers are recommended to download the BetaConcept program from VDRC (http://voronoi.hanyang.ac.kr) to explore the properties of the beta-shape.


Optimal ligand descriptor for pocket recognition based on the Beta-shape.

Kim JK, Won CI, Cha J, Lee K, Kim DS - PLoS ONE (2015)

A schematic diagram of a molecule and its beta-shape. Figure drawn by using the BetaConcept[44] and BetaMol program freely available from VDRC.(a) A two-dimensional molecule, (b) A two-dimensional molecule and its Connolly surface corresponding to the red circular probe, and (c) the beta-shape corresponding to the probe, (d) the van der Waals model of a protein (PDB id 1oq5), (e) the Connolly surface for water molecule (with 1.4Å radius), and (f) the corresponding beta-shape.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383629&req=5

pone.0122787.g001: A schematic diagram of a molecule and its beta-shape. Figure drawn by using the BetaConcept[44] and BetaMol program freely available from VDRC.(a) A two-dimensional molecule, (b) A two-dimensional molecule and its Connolly surface corresponding to the red circular probe, and (c) the beta-shape corresponding to the probe, (d) the van der Waals model of a protein (PDB id 1oq5), (e) the Connolly surface for water molecule (with 1.4Å radius), and (f) the corresponding beta-shape.
Mentions: For the proximity among the atoms on the molecular boundary, the concept of the beta-shape has been proposed [37]. Fig. 1(a) shows a two-dimensional molecule. Fig. 1(b) shows the Connolly surface (green curve) corresponding to the red circular probe where the radius is β. Suppose that the Connolly surface is straightened by substituting the straight edges for the circular arcs and the planar triangles for the spherical triangles where their vertices are the centers of the related atoms. The straightened object bounded by the planar facets is the beta-shape of the molecule. Fig. 1(c) shows the beta-shape of a molecule corresponding to the red circular probe in Fig. 1(b). The beta-shape concisely provides the precise proximity among the atoms on the molecular boundary with respect to the probe. Fig. 1(d), (e), and (f) show the van der Waals model of a protein (PDB id 1oq5), its Connolly surface for water molecule with 1.4Å radius, and the corresponding beta-shape. We note here that the beta-shape is efficiently computed from the quasi triangulation which is the dual structure of the Voronoi diagram of atoms. The details are reported in [37, 41–43] and readers are recommended to download the BetaConcept program from VDRC (http://voronoi.hanyang.ac.kr) to explore the properties of the beta-shape.

Bottom Line: Pocket recognition and definition is frequently a prerequisite of structure-based virtual screening, reducing the search space of the predicted protein-ligand complex.In this paper, we present an optimal ligand shape descriptor for a pocket recognition algorithm based on the beta-shape, which is a derivative structure of the Voronoi diagram of atoms.The performance of the proposed algorithm is verified by a benchmark test.

View Article: PubMed Central - PubMed

Affiliation: Voronoi Diagram Research Center, Hanyang University, Seoul, Korea.

ABSTRACT
Structure-based virtual screening is one of the most important and common computational methods for the identification of predicted hit at the beginning of drug discovery. Pocket recognition and definition is frequently a prerequisite of structure-based virtual screening, reducing the search space of the predicted protein-ligand complex. In this paper, we present an optimal ligand shape descriptor for a pocket recognition algorithm based on the beta-shape, which is a derivative structure of the Voronoi diagram of atoms. We investigate six candidates for a shape descriptor for a ligand using statistical analysis: the minimum enclosing sphere, three measures from the principal component analysis of atoms, the van der Waals volume, and the beta-shape volume. Among them, the van der Waals volume of a ligand is the optimal shape descriptor for pocket recognition and best tunes the pocket recognition algorithm based on the beta-shape for efficient virtual screening. The performance of the proposed algorithm is verified by a benchmark test.

No MeSH data available.