US 9,811,642 B2
Methods for shape comparison between drug molecules
Jun Xu, Guangzhou (CN)
Assigned to IPRECISION MEDICINE TECHNOLOGY, INC., Guangzhou (CN)
Appl. No. 14/351,978
Filed by Sun Yat-Sen University, Guangzhou (CN)
PCT Filed Nov. 16, 2012, PCT No. PCT/CN2012/084713
§ 371(c)(1), (2) Date Apr. 15, 2014,
PCT Pub. No. WO2014/012309, PCT Pub. Date Jan. 23, 2014.
Claims priority of application No. 2012 1 0245107 (CN), filed on Jul. 16, 2012.
Prior Publication US 2014/0278284 A1, Sep. 18, 2014
Int. Cl. G06F 17/50 (2006.01); G06F 7/60 (2006.01); G06F 17/10 (2006.01); G06F 19/00 (2011.01); G06F 19/16 (2011.01)
CPC G06F 19/706 (2013.01) [G06F 19/704 (2013.01); G06F 19/16 (2013.01); G06F 19/705 (2013.01)] 3 Claims
OG exemplary drawing
 
1. A method for shape comparison between drug molecules, comprising steps of:
(31) loading in three-dimensional structure information for a first molecule and a second molecule and calculating self-overlap volumes of the first and second molecules, the calculation comprising steps of:
loading in three-dimensional structure information of the first molecule, the three-dimensional structure information comprising type and coordinate values of each atom contained in the first molecule;
obtaining respective van der Waals radius based on the type of respective atom contained in the first molecule, converting the three-dimensional structure information into a group of Gaussian spheres representing atoms in the first molecule, each of the set of Gaussian spheres having a radius equal to the van der Waals radius of respective atom and a position equal to the coordinate position of respective atom;
calculating overlap volume for each pair of Gaussian spheres in the first molecule, wherein the ijth pair of Gaussian spheres in the first molecule consists of the ith and the jth Gaussian spheres and has a overlap volume vij;
calculating the weight of each Gaussian sphere in the first molecule, the weight of the ith Gaussian sphere in the first molecule

OG Complex Work Unit Drawing
wherein vi is the volume of the ith Gaussian sphere, and k is a constant;
calculating self-overlap volume of the first molecule

OG Complex Work Unit Drawing
wherein A is a set of all Gaussian sphere in the first molecule;
loading in three-dimensional structure information of the second molecule, the three-dimensional structure information comprising type and coordinate values of each atom contained in the second molecule;
obtaining respective van der Waals radius based on the type of respective atom contained in the second molecule, converting the three-dimensional structure information into a group of Gaussian spheres representing atoms in the second molecule, each of the set of Gaussian spheres having a radius equal to the van der Waals radius of respective atom and a position equal to the coordinate position of respective atom;
calculating overlap volume for each pair of Gaussian spheres in the second molecule, wherein the ijth pair of Gaussian spheres in the second molecule consists of the ith and the jth Gaussian spheres and has a overlap volume vij′;
calculating the weight of each Gaussian sphere in the second molecule, the weight of the ith Gaussian sphere in the second molecule

OG Complex Work Unit Drawing
wherein vi′ is the volume of the ith Gaussian sphere, and k′ is a constant;
calculating self-overlap volume of the second molecule

OG Complex Work Unit Drawing
wherein B is a set of all Gaussian sphere in the second molecule;
(32) calculating intermolecular volumes of the first and second molecules in various overlap situations, selecting the maximum intermolecular volume;
(33) determining the similarity between the first and second molecules based on the volume of the first molecule, the volume of the second molecule and the maximum intermolecular volume, the similarity being the result of the shape comparison between the two molecules; and
determining physical and chemical properties, and bioactivity of the two molecules according to the similarity between the first and second molecules so as to perform virtual screening of the drug molecules;
wherein the intermolecular volume of step (32) is a composite overlap volume between molecules, which is calculated by steps of:
finding out pharmacophores and their positions in each of the molecules;
determining types of each of the pharmacophores in each of the molecules;
calculating a self composite overlap volume

OG Complex Work Unit Drawing
of the first molecule, wherein Fij is the overlap volume between the ith pharmacophore and the jth pharmacophore, and the summation over Fij is limited only to pharmacophores of same type;
calculating a self composite overlap volume

OG Complex Work Unit Drawing
of the second molecule, wherein Fij′ is the overlap volume between the ith pharmacophore and the jth pharmacophore, and the summation over Fij′ is limited only to pharmacophores of same type;
calculating a composite overlap volume between the first and the second molecules

OG Complex Work Unit Drawing
wherein Fij″ is the overlap volume between the ith pharmacophore in the first molecule and the jth pharmacophore in the second molecule, and the summation over Fij″ is limited only to pharmacophores of same type;
calculating composite overlap volumes O12 between the first and the second molecules under various overlap situations and selecting the maximum value O12Max as the maximum intermolecular volume;
wherein step (33) specifically includes a step of calculating the similarity

OG Complex Work Unit Drawing
between the first and second molecules and outputting the similarity S12 as the result for the shape comparison for the two molecules.