In modelling applications, two basic kinds of charges are most frequently used: Formal charges and partial charges. There is a manifold of definitions for partial charges. Moreover, their proper determination is rather sophisticated and may even involve quantum chemical computations. Formal charges, on the other hand, can unambiguously be assigned on the basis of a few rules. Despite the fact that they do not reflect exact physics, they are in most cases the better choice for FlexX docking - on both ligand and protein.

FlexX is able to determine the necessary formal charges itself if the flag ASSIGN_FORMAL_CHARGES in config.dat is set to 1. If this flag is set to 0, FlexX uses the charges from the input file (e.g. the last column in the atom definition in a MOL2 file). Note that charges in the molecule files are most often partial charges: Thus, they cause inappropriate scores and consequently usually much worse placements! In order to be on the safe side for most cases ASSIGN_FORMAL_CHARGES should be set to 2, which is also the default. This mode takes the charges in the input file but issues an error message if charges seem to be partial charges. The automatic assignment of "formal charges" is initiated if this is the case. If the test is passed though, i.e., FlexX considers the charge entries as partial charges, no error message will be issued, and formal charges will not automatically be assigned. Please note: This is also the case if all input charges are zero, or if there are no charge entries in the input file at all!

Our recommendation is: Examine your input file to be really sure which charges are present and choose the appropriate mode for ASSIGN_FORMAL_CHARGES and ASSIGN_DELOCALised.

New in Release 2:
The assignment of formal charges, among others, is now handled by a new parameter, USE_TRANSFORMS in config.dat. If USE_TRANSFORMS is set to 1, the ligand passes through several levels of initialisation, which in turn are specified in a new static_data file, transform.dat:

Level 1		Correct valences and bonds in PDB structures [OFF]
Level 2		Preprocess / localize molecule [ON]
Level 3		Aromaticity check [ON]
Level 4		Assign default protonation [ON]
Level 5		Assign formal charges [ON]
Level 6		Assign delocalized systems [ON]
Level 10		Assign atom-types [ON]

The flag ASSIGN_FORMAL_CHARGES is still kept for backwards compatibility, but will be removed in one of the following versions of FlexX. For the time being, the flag, together with USE_TRANSFORMS still has to be set to 1 in the config.dat,in order to invoke the assignment of formal charges to the ligand.
As an alternative, this can also be controlled from the command line under the LIGAND submenu in FlexX as shown below. The setting in the config.dat file will then be overwritten.

Type 'SELINIT' and then the number of the level you would like to turn on, or 'SELINIT !' and the number of the level you would like to turn off. E.g. 'SELINIT 5' would turn on, 'SELINIT !5' would turn off the assignment of fromal charges to the ligand.