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Influence of conformation on the representation of small flexible molecules at low resolution: alignment of endothiapepsin ligands

“…In previous applications of low resolution molecular representations to the comparison of small molecules, we considered rigid benzodiazepinerelated structures and thrombin inhibitors [11][12][13][14][15]. Here, a new set of five highly flexible endothiapepsin ligands was selected after the very interesting work of Lemmen et al [45].…”

“…In previous works, we applied the program OR-CRIT [60] to generate critical point (CP) graph representations of molecules from their smoothed ED distributions, and we used the resulting graph representations for molecular alignment purposes [11][12][13][14][15]. These graphs consisted in a set of CPs located in molecular ED that were calculated at medium crystallographic resolution, or that were smoothed using various mathematical tools such as wavelet analysis or by application of the diffusion equation.…”

“…As already mentioned, we used the procedure that was already applied previously [13][14][15], i.e., a MC/SA method for the pairwise matching of the molecular CP graphs obtained from the molecular structures at various resolutions. Molecular conformers are represented using local ED properties, i.e., the ED values associated with the peaks, and their inter-distances.…”

“…In previous works of our group [11][12][13][14][15], both GA and Monte Carlo/Simulated Annealing (MC/ SA) algorithms were applied to the alignment of small biomolecules in a given conformation using topographical information extracted from their ED distribution. The particularity of our works resides in the use of low resolution ED distributions to generate reduced graph representations, i.e., representations above the atomic level.…”

Similarity measures based on Gaussian‐type promolecular electron density models: Alignment of small rigid molecules

“…10,27 We have exploited this last advantage in recent works on molecular superposition approaches based on multiresolution CP analyses of molecular ED distributions. [28][29][30] In those works, it was shown how graph representations of low resolution ED distributions of molecular structures could be used to easily compare different drug-like molecules. These graph representations, composed of vertices and edges that were generated using an AIM-related CP analysis of low resolution ED maps, led to pharmacophore-type models of biological molecules.…”