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 YatSen 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 
1. A method for shape comparison between drug molecules, comprising steps of:
(31) loading in threedimensional structure information for a first molecule and a second molecule and calculating selfoverlap
volumes of the first and second molecules, the calculation comprising steps of:
loading in threedimensional structure information of the first molecule, the threedimensional 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 threedimensional 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 ij^{th }pair of Gaussian spheres in the first molecule consists of the i^{th }and the j^{th }Gaussian spheres and has a overlap volume v_{ij};
calculating the weight of each Gaussian sphere in the first molecule, the weight of the ^{ith }Gaussian sphere in the first molecule
calculating selfoverlap volume of the first molecule
loading in threedimensional structure information of the second molecule, the threedimensional 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 threedimensional 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 ij^{th }pair of Gaussian spheres in the second molecule consists of the i^{th }and the j^{th }Gaussian spheres and has a overlap volume v_{ij}′;
calculating the weight of each Gaussian sphere in the second molecule, the weight of the i^{th }Gaussian sphere in the second molecule
calculating selfoverlap volume of 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
calculating a self composite overlap volume
calculating a composite overlap volume between the first and the second molecules
calculating composite overlap volumes O_{12 }between the first and the second molecules under various overlap situations and selecting the maximum value O_{12}^{Max }as the maximum intermolecular volume;
wherein step (33) specifically includes a step of calculating the similarity
