Declustering potential and collision energies for each folate standard were optimised for compound-dependent parameters using the quantitative optimisation wizard of the Analyst software (version 1.4.2).
The MS MS fragmentation conditions were optimised for each compound in order to obtain both specific fragments and high signal intensity.
Alternatives to gain the needed sensitivity are cleanup and enrichment of aflatoxins (e.g. by immunoaffinity columns), a method parameter set which is optimised on those compounds, or the use of a more sensitive mass spectrometer [ 33].
The series was optimised rapidly to a compound showing oral activity in an in vivo disease model.
The best scoring poses for each compound were optimised in their docked state by half a rotation and translation step in each direction using the OEChemScore scoring function.
In the context of virtual screening this is very likely to affect the performance of the method because some pharmacophoric features are rarer than others, particularly in compound libraries optimised for drug-likeness.
The MS/MS fragmentation conditions and collision energies were optimised for each individual compound to give the best response.
This means that a compound with optimised stability properties may still be unusable as a radiopharmaceutical component if a high yield of radiolabelling cannot be achieved under suitable conditions and on an appropriate timescale.
25 The reactions contained 7.5 n m TbGSK3, 3.2 μ m substrate peptide (Pepceuticals), 1 μ m ATP, and 25 μ m test inhibitor compound in optimised kinase assay buffer.
The EEM parameters for carbon, nitrogen, oxygen and hydrogen were derived by using the fitting procedure described by Njo et al.[14] The EEM parameters for the organic compounds were optimised to reproduce the MKS charges for proteins as reported by Cornell et al.[15] Fig. 1 shows the reproduction of the MKS protein charge distributions using the optimised EEM parameters (Table 1).
