Contour� is Vitae's proprietary structure-based drug design technology that comprises a context perceptive growth algorithm and a contact sensitive scoring function. The grown molecules are ranked by a unique electronic environment and contact direction sensitive scoring function. The latest version of the scoring function has novel features. On the basis of molecular orbital theory, each atom is modeled by features, called zones, explicitly representing electron lone pairs, p-orbitals, and polar and non-polar hydrogens, etc. The quantum based CM1A charge was computed for each atom and partitioned to each zone. Contour scoring function computes the interaction energy and the desolvation effect of the protein-ligand association energy as a linear sum of pair-wise interactions and desolvation terms. The pair-wise interaction energy determination was designed with the emphasis on capturing short-range positive electrostatic interactions, such as hydrogen bonds with stringent geometric requirements.  The desolvation energy is estimated by calculating the energy required to desolvate interaction surfaces of the protein and the ligand zones in the complex. The scoring function achieved an R2 of 0.73 on the training set, and performed the best along with three other scoring functions on a diverse set of proteins from PDBbind. It is equivalent to the MM-GBSA method in predicting congeneric BACE1 complexes.

Unique contact direction sensitive scoring function for predicting protein-ligand binding in Contour<sup>�</sup>

248th National Meeting (2014)

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Unique contact direction sensitive scoring function for predicting protein-ligand binding in Contour�

Unique contact direction sensitive scoring function for predicting protein-ligand binding in Contour^�