Method and system to build optimal models of 3-dimensional molecular structures

• US 7,158,891 B2
• Filed: 03/28/2002
• Issued: 01/02/2007
• Est. Priority Date: 03/26/2002
• Status: Expired due to Fees

• Current Assignee: Council of Scientific & Industrial Research
• Original Assignee: Council of Scientific & Industrial Research
• Inventors: Gautham, Namasivayam, Vengadesan, Krishnan
• Primary Examiner(s): Zeman; Mary K.
• Application Number:
  US10/113,219
• Publication Number:
  US 20030187585A1
• Time in Patent Office: 1,741 Days
• Field of Search: 703/2, 703/11, 703/12, 707/102, 708/207
• US Class Current: 702/20
• CPC Class Codes: G16B 15/00 ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment
• CPC Class Codes: G16C 20/50 Molecular design, e.g. of drugs
• CPC Class Codes: Y10S 707/99943 Generating database or data structure, e.g. via user interface

Abstract

The present invention relates to a method to build 3-dimensional models of molecular structures corresponding to the lowest value of the potential energy function from knowledge of their chemical structures. The system uses Mutually Orthogonal Latin Squares to search through conformational space to obtain the best conformation. The system may also be used to obtain the optimum of any function, and not only those related to biomolecular structure.

Claims

1. A method for modeling the three dimensional structure of a molecule by determining the lowest value of conformational potential energy of a molecule by using an algorithm to define the lowest value of the conformational potential energy as the best conformation representing the three dimensional structure of the molecule, said algorithm comprising the steps of:

a) representing the molecule in terms of coordinates defined by torsion angles of the atoms comprising the molecule;

b) specifying the number of torsion angles, n, the range of each n torsion angle, and a step size at which the values of each torsion angle is sampled, there being a total of m steps for each torsion angle, θ

_r,s,r=1 to n and s=1 to m as the input set of values for each torsion angle selected;

c) selecting a set of all possible conformations of the molecule represented by a combinatorial arrangement of Mutually Orthogonal Latin Squares (MOLS) of order N, wherein said MOLS are constructed based upon the n selected torsion angles of the molecule to provide N² sub squares in each set of MOLS, wherein N is a prime number obtained by R/m, R being 360°

, with each MOLS sub square corresponding to one possible conformation of the molecule;

d) labeling the sub squares of the MOLS by indices (u,t), u and t being integer numbers, u=1 to N and t=1 to N, and the value of the rth torsion angle in a given sub square (u,t) being chosen from the input set of values θ

_r,s as

2. A method according to claim 1, wherein a single best value for the torsion angle is used to calculate the indices (u,t) for labeling the MOLS sub squares, the potential energy

3. A method according to claim 1 wherein the molecule is a small molecule selected from the group consisting of peptides and nucleotides.

4. A method according to claim 1 wherein the molecule is a macromolecule selected from the group consisting of proteins and polynucleic acids.

5. A method according to claim 1 wherein the calculations are conducted in parallel by employing several computers for the calculations.