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[ Table to Template Superposition | Rigid Substructure Superposition | Flexible Substructure Superposition | APF Superposition | Multiple APF Superposition ]
Chemical superposition can be undertaken in the following ways.
The substructure superposition requires topologically exact match with the template. As long as there is a large consistent scaffold then the substructure superposition is the best approach. In cases where the structures differ topologically then the APF methods should be used to superimpose moieties which have similar properties.
17.18.1 Rigid Superposition of Compounds in a Table onto a Template in The Graphical Display |
NOTE: The substructure superposition requires topologically exact match with the template. As long as there is a large consistent scaffold then the substructure superposition is the best approach. In cases where the structures differ topologically then the APF methods should be used to superimpose moieties which have similar properties. |
Here we describe how to superimpose chemicals from an ICM Molecular Table onto a 3D template displayed in the graphical display.
17.18.2 Rigid Substructure Superposition |
NOTE: The substructure superposition requires topologically exact match with the template. As long as there is a large consistent scaffold then the substructure superposition is the best approach. In cases where the structures differ topologically then the APF methods should be used to superimpose moieties which have similar properties. |
Here we describe how to perform a rigid-superposition of chemical structures in the graphical display:
NOTE: Superimposed chemicals can be separated easily using the Arrange as grid option. This option can be found in the Chemisty menu Chemistry/Arrange as Grid. |
17.18.3 Flexible Substructure Superposition |
NOTE: The substructure superposition requires topologically exact match with the template. As long as there is a large consistent scaffold then the substructure superposition is the best approach. In cases where the structures differ topologically then the APF methods should be used to superimpose moieties which have similar properties. |
Here we describe how to perform a flexible-superposition of chemical structures in the graphical display:
NOTE: Superimposed chemicals can be separated easily using the Arrange as grid option. This option can be found in the Chemisty menu Chemistry/Arrange as Grid. |
17.18.4 Flexible APF Superposition to Template from Table |
NOTE: The APF superposition method should be used when there is no common substructure between the chemicals that are being superimposed. If a common substructure is present then the substructure superposition methods described earlier should be used. The APF method will superimpose moieties that similar properties. |
The Atomic Property Fields (APF) superposition/alignment method was reported by Maxim Totrov PhD (Principal Scientist - MolSoft) at the 2007 233rd American Chemical Society National Meeting, Chicago, IL USA (see: http://oasys2.confex.com/acs/233nm/techprogram/P1057814.HTM). APF is a 3D pharmacophoric potential implemented on a grid. APF can be generated from one or multiple ligands and seven properties are assigned from empiric physico-chemical components (hydrogen bond donors, acceptors, Sp2 hybridization, lipophilicity, size, electropositive/negative and charge).Here we describe template APF superposition whereby the APF is generated from a single or multiple template and is then globally optimized with the internal force-field energy of the ligand. The optimization is undertaken using the ICM Biased Probability Monte-Carlo method described in Abagyan and Totrov JMB 1994.
To perform Flexible APF Superposition:
17.18.5 Multiple APF Alignment of Compounds in a Table |
NOTE: The APF superposition method should be used when there is no common substructure between the chemicals that are being superimposed. If a common substructure is present then the substructure superposition methods described earlier should be used. The APF method will superimpose moieties that similar properties. |
APF is briefly described in the previous section describing flexible APF superposition to a template. In the Multiple APF alignment method an initial superposition is generated by superimposing the inertia ellipsoids of all ligands in random conformations and then the total APF is generated on a grid. Each molecule is then optimized in the APF fields by ICM Biased Probability Monte-Carlo method described in Abagyan and Totrov JMB 1994. The procedure is repeated until a self-consistent field is acheieved.
To superimpose multiple chemicals in a chemical table by the APF method:
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