MolShaCS: A free and open source tool for ligand similarity identification based on Gaussian descriptors

Autor(es)

Vaz de Lima, Luis Antonio C. ^[1] ; Nascimento, Alessandro S. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Engn Modelagem & Ciencias Sociais Aplicadas, BR-09210170 Sao Paulo - Brazil

^[2] Inst Fis Sao Carlos, Grp Biotecnol Mol, BR-13560970 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 59, p. 296-303, JAN 2013.
• Citações Web of Science: 12

Resumo

Molecular similarity evaluation is an important step in most drug development strategies, since molecular similarity is usually related to functional similarity. Here, we developed a method based on the Gaussian description of molecular shape and charge distribution for molecular similarity identification. The method was evaluated using the Directory of Useful Decoys (DUD) and a retrospective test. Enrichment factors computed for DUD targets showed that the proposed method performs very well in recognizing molecules with similar physicochemical properties and dissimilar topologies, reaching an average AUC of 0.63 and enrichment factor of 10 at 0.5% of decoys. A retrospective test also showed that nine mineralocorticoid ligands were ranked among the top ten molecules in a search of a database of approved drugs for molecules similar to aldosterone. Altogether, these data show that the Gaussian-based description of molecular shape and charge distribution implemented in the program MolShaCS is an efficient method for molecular similarity identification. The program is publicly available at the address http://www.ifsc.usp.br/biotechmol. (C) 2012 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 10/15376-8 - Estudo prospectivo de ligantes do receptor PPAR gama
• Beneficiário: Alessandro Silva Nascimento
• Modalidade de apoio: Auxílio à Pesquisa - Regular