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Smoothed Gaussian molecular fields: an evaluation of molecular alignment problems

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Abstract

Several smoothed Gaussian-based descriptors used in a molecular superposition algorithm are presented. One descriptor, as detailed in a previous work (Leherte in J Comput Chem 27:1800–1816, 2006), is the full electron density approximated through the promolecular atomic shell approximation (PASA) (Amat and Carbó-Dorca in J Chem Inf Comput Sci 40:1188–1198, 2000). Herein, we additionally present a new descriptor, that is, the charge density of a molecule calculated via the Poisson equation. The Coulomb potential as approximated by Good et al. (J Chem Inf Comput Sci 32:188–191, 1992) and atom-based functions such as hydrogen bond donor or acceptor properties, lipophilicity as detailed in the work of Totrov (Chem Biol Drug Des 71:15–27, 2008) were also considered. A Monte Carlo/Simulated Annealing superposition method is applied to a set of six families of drug molecules, that is, elastase inhibitors, ligands of endothiapepsins, trypsins, thermolysins, p38 MAP kinases, and rhinovirus, all of them already reported in the literature, for discussing superposition problems. The results show that the descriptor selection can be guided by the nature of the interactions expected to occur between the drug molecules and their receptor. They also emphasize the particular efficiency of the PASA descriptor for molecules characterized by significant shape properties.

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Acknowledgments

The authors thank the reviewers for their comments. They also acknowledge L. Piela for fruitful discussions, the support of the F.R.S.–F.R.F.C. (convention no. 2.4.617.07.F), and the ‘‘Facultés Universitaires Notre-Dame de la Paix’’ (FUNDP) for the use of the Interuniversity Scientific Computing Facility (ISCF) Center.

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  1. Laboratoire de Physico-Chimie Informatique, Unité de Chimie Physique Théorique et Structurale, Facultés Universitaires Notre-Dame de la Paix (FUNDP), Rue de Bruxelles 61, 5000, Namur, Belgium

    Laurence Leherte & Daniel P. Vercauteren

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  1. Laurence Leherte
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  2. Daniel P. Vercauteren
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Correspondence to Laurence Leherte.

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Published as part of the special collection of articles celebrating theoretical and computational chemistry in Belgium.

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Leherte, L., Vercauteren, D.P. Smoothed Gaussian molecular fields: an evaluation of molecular alignment problems. Theor Chem Acc 131, 1259 (2012). https://doi.org/10.1007/s00214-012-1259-y

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