FieldTemplater

Options

Basic

Column containing input molecules

The column in the input datatable containing 2-10 input molecules.

Speed

Speed of operation of FieldTemplater. Choose from (in order of decreasing speed, but increasing thoroughness): Quick, Normal or Normal (large mols). Note that changing this option will alter the values of several other options.

Assign formal charges to input molecules

If checked, the protonation states for the input molecules are set using Cresset's charging rules. Acids will be deprotonated, primary amines protonated, etc.

Conformer Hunt

Generate at most this number of conformations

The maximum number of conformations to produce per input molecule. Values of 50-200 are recommended and a maximum of 1000 can be set.

No. of high-T dynamics runs for flexible rings

Most small rings are handled using a ring conformation library. Conformations for rings that are not found in the library are sampled using high-temperature (~600K) dynamics with energy initially distributed into torsional degrees of freedom. The number of dynamics runs (and hence the degree of ring conformation sampling) is set by this value. Values of 2-10 are recommended. Values above 5 make little difference to flexible rings of fewer than 8 atoms.

Gradient cut-off for conformer minimization

All conformers found are minimized using the XED force field. This option sets the gradient cut-off at which the minimization is terminated. Values that are too small lead to insufficient sampling of conformational space and long run times. Values that are too large can lead to unrealistic structures being generated. Values of 0.1 kcal/mol/A to 1.0 kcal/mol/A are recommended with values at the smaller end of the range being preferred if the 'Include coulombics' option is not checked.

Energy window

Conformations that have a minimized energy that is outside the energy window are discarded. The window is calculated from the lowest energy conformation that has been found. The ideal value for this option depends on the 'gradient cut-off for conformer minimization' and 'Include coulombics' options. The best results when the 'Include coulombics' option is not checked are obtained by minimizing to a low gradient (0.1 or better) and applying a smaller energy window (3 kcal/mol) but this significantly increases the time for the calculation. Checking the 'Include coulombics' option requires a significantly larger energy window for large molecules (12 kcal/mol) as these can form very low energy collapsed and internally H-bonded structures.

RMS filter for conformation generation

Sets the similarity threshold below which two conformers are deemed identical. This effectively controls the coarseness of the sampling of conformational space. A low value leads to conformations that are only marginally different, while using a large value means that a conformation near the 'correct' one may not be generated. Values of 0.5 A to 1.0 A are recommended: values at the higher end of the range are more appropriate for larger, more flexible molecules.

Acyclic secondary amides handling

Specify how the conformation hunter is to handle amides. Note that this option has no effect on ureas, urethanes, and thioamides as the N-C bonds in these are always treated as rotatable.

• Force amides trans - forces all secondary amides to adopt the trans geometry.
• Use input amide geometry - leaves secondary amides in the geometry that they were in the input file and sets them as non-rotatable. As a result, if the input molecule was drawn with a cis amide then only conformations with cis amides will be generated.
• Allow amides to spin - allows the amide bind to spin, so a mixture of cis and trans amides can be generated.

Include coulombics

If checked, then the conformer generation process uses the full force field, including long-range electrostatics. Better conformer populations are usually generated with this turned off.

Alignment

Shape weight

The relative weight assigned to shape (as opposed to field) similarity. Values must be between 0.0 (all field) and 1.0 (all shape).

Conformers of achiral molecules can be inverted

Allows conformers of achiral molecules to be inverted if that gives a better alignment. Chiral molecules are never inverted. This must be checked if the imported conformations were exported from Forge, as the conformer population filters out mirror image conformations.

Atom constraints

Consists of m1,a1,m2,a2,d1[,d2][,s] where

• m1 = index of molecule 1
• a1 = index of the atom in molecule 1
• m2 = index of molecule 2
• a2 = index of the atom in molecule 2
• d1 = minimum distance between the atoms in Angstroms
• d2 = maximum distance between the atoms in Angstroms, same as d1 if not specified
• s = the constraint strength in A^-2

e.g. 1,1,2,5,2.0 means a constrains atom 1 on molecule 1 and atom 5 on molecule 2 to be 2.0A away from each other, constraint strength 10 A^-2. You may have more than one atom constraint specified, separated by newlines. See the Forge manual for a detailed explanation of atom constraints.

Templating

Minimum molecules per Template

The minimum number of molecules which are required to form a template. With 5 molecules, set this to 5 to only find templates containing 5 molecules.

Maximum molecules per Template

The maximum number of molecules in a template. With 5 molecules, set this to 4 to only find templates with 4 or fewer molecules present. To find all templates with 3 to 5 molecules present, set minimum molecules per template to 3 and maximum molecules per template to 5.

Generate at most this number of pairwise alignments

Up to 1000 alignments are generated between each pair of molecules, sorted by score. In general, the best results are obtained if only the highest-scoring alignments are used in the templating process. This value controls the maximum number of alignments that will be used from any pair in forming a template. Values of 100-200 are recommended. Higher values usually give more templates. This setting is cumulative with the 'Maximum score delta per pair' limit in that the more restrictive setting will be applied for any pair of molecules.

Maximum score delta per pair

Set the maximum difference in score between the best alignment of any given pair of molecules and the worst alignment used in the templating step. For example, with the default value of 0.1, if the best-scoring alignment of molecules A and B has a score of 0.7, then no alignment of A and B with a score less than 0.6 will be used to generate the templates. Again, higher values give more templates. A range of 0.05 to 0.2 is recommended. This setting is cumulative with the 'Generate at most this number of pairwise alignments' setting as the more restrictive will be applied for any pair of molecules.

Minimum link density in a template

The minimum fraction of possible pairwise links that must be used in constructing this template. For example, in a 5-molecule template there are 10 pairs of molecules. A template constructed using 8 pairwise alignments (so that 2 pairs were 'missing') has a density of 0.8, so would not be allowed if this parameter was greater than 0.8. Lower values are recommended for larger sets of molecules (5 or more) where no templates are found. However, please note that templates with a low link density are less reliable.

Filter duplicate templates at RMS

If two templates containing the same conformers of the same molecules are found, then remove the lower-scoring one if they are closer than this limit.

Advanced

Add calculation logs as columns

If checked, the log of the conformer generation and alignment process for each molecule is added as columns 'Molecule_Log' and 'Template_Log'.

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