In model refinement, XVOLs and a molecular shape constraint derived from the highly active compound 1 in its conformation that optimally fit the highest ranked model were added as steric restrictions.
Orientational restraints included in refinement were derived from residual dipolar couplings measured in a liquid crystalline medium containing bacteriophage Pf1, and a restraint on overall molecular shape was imposed from SAXS data (additional SAXS data are presented in Supplementary Figure S3 at http://www.BiochemJ.org/bj/445/bj4450361add.htm).htm
In a typical application, Spectrophores™ are calculated from the molecular shape in combination with the electrostatic, lipophilic, softness, and hardness potential surrounding the molecules.
The program MODULE was used to calculate the alignment tensor from the CXCL12α molecular shape and evaluate the correlations between experimental and backcalculated RDCs [40].
It is impossible for the crosslinking reaction to form a trimer without forming a dimer; thus, we did not consider that the peak corresponded to a trimer but instead, speculated that the shift resulted from an extended molecular shape.
Previous studies have shown that one of the key features in discriminating active from inactive molecules is molecular shape [18, 19].
The poorer performance at this level (>12) can be attributed to the noise resulting from far too detailed a description of the molecular shape.
Residual dipolar couplings were calculated from the ensemble using a method based on molecular shape, described previously, in combination with a generalized alignment tensor.
We start from the molecular interaction and the molecule fluid friction, and write down a general formulation based on the molecular shape and the free energy.
Thus, from a 3DZD point of view, these inactives are closer in the molecular shape to the query than the actives.
