Systems and methods for making two dimensional graphs of complex molecules

Patent metadata

Field	Value
Publication number	US-10168885-B2
Application number	US-201415023532-A
Country	US
Kind code	B2
Filing date	Sep 17, 2014
Priority date	Mar 21, 2012
Publication date	Jan 1, 2019
Grant date	Jan 1, 2019

Abstract

Systems and methods for visualization of a molecule, comprising a set of particles, are provided. A set of three-dimensional coordinates is obtained, each coordinate describing a position for a corresponding particle. A cost function containing an error in a set of two-dimensional coordinates, where each two-dimensional coordinate corresponds to a three-dimensional coordinate in the set of three-dimensional coordinates, is minimized until an exit condition is achieved. The minimization alters the two-dimensional coordinate values. A set of physical properties S M is obtained, each such property representing a property shared by a pair of particles in the molecule. The coordinates are plotted as nodes of a two-dimensional graph after minimization, connected by a plurality of edges. An edge connects a coordinate pair in the graph that corresponds to a pair of particles in the molecule. A characteristic of the edge is determined by a physical property for the pair of particles.

First claim

What is claimed is:

1. A computer-implemented method for visualizing physical properties of a molecule in two dimensions, wherein the molecule comprises a set of {p 1 , . . . , p N } particles, each particle p i in the set of particles representing a different plurality of covalently bound atoms in the molecule, the method performed on a first computer system having at least one processor and memory storing at least one program for execution by the at least one processor to perform the method, comprising:
(A) obtaining a set of N three-dimensional coordinates {x 1 , . . . , x N } by x-ray crystallography, nuclear magnetic resonance spectroscopic techniques, electron microscopy, modeling or from a non-transitory computer readable storage medium, wherein each respective x i in {x 1 , . . . , x N } corresponds to a p i in {p 1 , . . . , p N } and represents the position of p i in three-dimensional space, wherein N is a positive integer of greater than 30;
(B) minimizing a cost function containing an error in a set of two-dimensional coordinates corresponding to the set of N three-dimensional coordinates using a minimization function module:

E
⁡

(

c
1

,

c
2

,
…
⁢

,

c
N

)

=

∑

i
<
j

N

⁢

⁢

w
ij

⁢



δ
ij

-

D
⁡

(

c
i

,

c
j

)



2

using the set of N three-dimensional coordinates wherein,
i and j are integers greater than zero,
δ ij is a distance between a pair of three-dimensional coordinates x i and x j in {x 1 , . . . , x N },
E(c 1 , c 2 , . . . , c N ) is an error in the set of two-dimensional coordinates (c 1 , c N ), wherein each two-dimensional coordinate c i in (c 1 , c N ) uniquely corresponds to a three-dimensional coordinate x i in {x 1 , . . . , x N } so that each respective p i in {p 1 , . . . , p N } is represented by a three-dimensional coordinate x i in {x 1 , . . . , x N } and a corresponding two-dimensional coordinate c i in (c 1 , . . . , c N ),
D(c i , c j ) is a distance between the two-dimensional coordinates c i and c j in (c 1 , . . . , c N ), and
w ij is a weight for the two-dimensional pair (p i , p j ) in a matrix of weights, wherein the matrix of weights has a weight for each two-dimensional pair (p i , p j ) in (p 1 , . . . , p N ),

wherein the minimizing alters the values of coordinates of the set of two-dimensional coordinates (c 1 , . . . , c N ) using a refinement algorithm until an exit condition is achieved;
(C) obtaining a plurality of sets of physical properties S Mk from a non-transitory computer readable storage medium, each physical property s i,j in S Mk representing a respective physical property k shared by a pair of particles (p i , p j ) in {p 1 , . . . , p N } in the molecule;
(D) plotting (c 1 , . . . , c N ), with a graphical user interface, after the exit condition is achieved, as a plurality of nodes of a two-dimensional graph; and
(E) plotting, with the graphical user interface, a first plurality of edges for the two-dimensional graph, wherein
each respective edge in the first plurality of edges connects a two-dimensional coordinate pair (c i , c j ) in the graph that corresponds to a pair of particles (p i , p j ) in {p 1 , . . . , p N }, and
a first characteristic of each respective edge in the first plurality of edges is determined by a respective physical property s i,j in S M1 for the pair of particles (p i , p j ) in {p 1 , . . . , p N } corresponding to the two-dimensional coordinate pair (c i , c j ) that is connected by the respective edge.

2. The computer-implemented method of claim 1 wherein k is a positive integer of 2 or greater.

3. The computer-implemented method of claim 1 wherein the plotting (E) is done on a conditional basis in which each respective edge in the first plurality of edges is conditionally plotted as a function of the respective physical property s i,j in S M1 for the pair of particles (p i , p j ) in {p 1 , . . . , p N } corresponding to the two-dimensional coordinate pair (c i , c j ) that is connected by the respective edge.

4. The computer-implemented method of claim 3 , wherein:
a first edge in the first plurality of edges is not plotted by the plotting (E) when the physical property s i,j does not satisfy a first threshold condition, and
the first edge is plotted by the plotting (E) when the physical property s i,j satisfies the first threshold condition.

5. The computer-implemented method of claim 4 , wherein a histogram of values for the physical property s i,j of S M1 are displayed and the first threshold condition is determined by a selection of a subset of the histogram of values.

6. The computer-implemented method of claim 5 , wherein the first threshold condition is satisfied when a value of the physical property s i,j is outside the subset of the histogram values.

7. The computer-implemented method of claim 5 , wherein the first threshold condition is satisfied when a value of the physical property s i,j is within the subset of the histogram of values.

8. The computer-implemented method of claim 5 , wherein the subset of the histogram values is user adjustable using mouse cursor functions.

9. The computer-implemented method of claim 1 , wherein the plotting (E) further comprises:
plotting a second plurality of edges for the two-dimensional graph, wherein
each respective edge in the second plurality of edges connects a two-dimensional coordinate pair (c i , c j ) in the graph that corresponds to a pair of particles (p i , p j ) in {p 1 , . . . , p N }, and
a first characteristic of each respective edge in the second plurality of edges is determined by a respective physical property s i,j in S M2 for the pair of

Assignees

• Zymeworks Inc

Inventors

• Ohrn Anders
• Macdonald Scott Paul

Classifications

• G06F3/04847 Primary

  Interaction techniques to control parameter settings, e.g. interaction with sliders or dials · CPC title

• G06F19/70

  Physics · mapped topic

• G06T15/10

  Geometric effects · CPC title

• G16C20/80 Primary

  Data visualisation · CPC title

• G16C99/00

  Subject matter not provided for in other groups of this subclass · CPC title