Method and System of Estimating the Cross-Sectional Area of a Molecule For Use in the Prediction of Ion Mobility

Patent metadata

Field	Value
Publication number	US-2015379242-A1
Application number	US-201514733191-A
Country	US
Kind code	A1
Filing date	Jun 8, 2015
Priority date	Apr 5, 2009
Publication date	Dec 31, 2015
Grant date	—

Abstract

A method of estimating the cross-sectional area of a molecule for use in the prediction of ion mobility gives gas phase interaction radii determination and cross-sectional algorithm computation to provide separation and characterisation of structurally related isomers. More specifically, the invention provides a method of correlating the differences in the molecular structures with differences in anti-cancer activity of pre-determined anti-cancer drugs by utilizing a new algorithm for estimating the cross-sectional area of the molecules of such drugs.

First claim

1 . A method of estimating a cross sectional area of a molecule of interest with a processor comprising the steps of:
A) Assigning, by the processor, an ellipsoidal boundary containing all of said molecule of interest; B) Selecting, by the processor, an orientation of the assigned ellipsoidal boundary together with the molecule of interest; C) Calculating, by the processor, a value for an area contained by an elliptical boundary formed by a projection of the ellipsoid at said selected orientation; D) Selecting, by the processor, a position within the elliptical boundary; E) Identifying, by the processor, whether the position within the elliptical boundary also falls within the cross sectional area of an atom within the molecule of interest; F) If said position within the elliptical boundary also falls within the cross sectional area of any atom within the molecule of interest then setting, by the processor, said cross sectional area of the molecule at said orientation to the cross sectional area contained by the elliptical boundary calculated in step C, if said position within the elliptical boundary does not fall within the cross sectional area of the atom within the molecule of interest then setting, by the processor, said cross sectional area of the molecule to 0; G) Calculating, by the processor, an averaged cross sectional area over all said selected orientations wherein at least steps F) and G) are preformed with the processor; H) Iterating, by the processor, steps C) to G) for at least N iterations or until M independent calculations of the averaged cross sectional area agree within a predetermined range R for X iterations.

2 . A method according to claim 1 , wherein the value of N is between 1-50.

3 . A method according to claim 1 , wherein the value of M is between 1-20.

4 . A method according to claim 1 , wherein the value of R is between 1 and 20%.

5 . A method according to claim 1 , wherein the value of X is between 1 and 20.

6 . A method according to claim 1 further comprising determining characteristics of predetermined molecules comprising the use of a combined ion mobility-mass spectrometry (IM-MS) technique for experimentally determining a range of molecular structures and
comparing the characteristics determined with the mass spectrometry technique with those derived by the estimating the cross sectional area of a molecule of interest so as to correlate the differences in the molecular structures with differences in selected predetermined activity of those molecules.

7 . A method according to claim 6 wherein the method correlates the differences in the molecular structures with differences in anti-cancer activity of predetermined anti-cancer drugs.

8 . A method according to claim 7 wherein the anti-cancer drugs are organometallic based drugs.

9 . A method according to claim 8 wherein the organometallic drugs are isomeric Ru-based.

10 . A method according to claim 7 , wherein the IM-MS technique includes the use of travelling wave (T-wave) mobility separation.

11 . A system for determining characteristics of predetermined molecules, the system comprising an ion mobility cell, a mass spectrometer and a processor programmed or configured to determine experimentally a range of molecular structures and compare values of that range with those derived by a method of estimating a cross sectional area of a molecule of interest, said the system further comprising a non-transitory computer readable medium having a computer program executed by said processor to perform the steps of:
A) Assigning an ellipsoidal boundary containing all of said molecule of interest; B) Selecting an orientation of the assigned ellipsoidal boundary together with the molecule of interest; C) Calculating a value for an area contained by an elliptical boundary formed by a projection of the ellipsoid at said selected orientation; D) Selecting a position within the elliptical boundary; E) Identifying whether the position within the elliptical boundary also falls within the cross sectional area of an atom within the molecule of interest; F) If said position within the elliptical boundary also falls within the cross sectional area of any atom within the molecule of interest then setting said cross sectional area of the molecule at said orientation to the cross sectional area contained by the elliptical boundary calculated in step C, if said position within the elliptical boundary does not fall within the cross sectional area of the atom within the molecule of interest then setting said cross sectional area of the molecule to 0; G) Calculating an averaged cross sectional area over all said selected orientations wherein at least steps F) and G) are preformed with the processor in the system; H) Iterating steps C) to G) for at least N iterations or until M independent calculations of the averaged cross sectional area agree within a predetermined range R for X iterations so as to correlate the differences in the molecular structures with differences in selected predetermined activity of those molecules.

12 . A computer program element comprising computer readable program code means for causing a processor to execute a procedure to implement the method of claim 1 .

13 . Computer program element according to claim 12 embodied on a computer readable medium.

14 . A computer readable medium having a program stored thereon, where the program is to make a computer execute a procedure to implement the method of claim 1 .

Assignees

• Micromass Ltd

Inventors

• Richardson Keith George
• Campuzano Iain David Grant

Classifications

• G01N27/623

  combined with mass spectrometry · CPC title

• G06F19/701 Primary

  Physics · mapped topic

• G06F17/18

  for evaluating statistical data {, e.g. average values, frequency distributions, probability functions, regression analysis (forecasting specially adapted for a specific administrative, business or logistic context G06Q10/04)} · CPC title

• G16B15/00

  ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment · CPC title

• G16C20/30

  Prediction of properties of chemical compounds, compositions or mixtures · CPC title