Fast Small Molecule Similarity Searching with Multiple Alignment Profiles of Molecules Represented in One-Dimension
- 30 September 2005
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 48 (22) , 6980-6990
- https://doi.org/10.1021/jm050563r
Abstract
Multiple sequence alignment has proven to be a powerful method for creating protein and DNA sequence alignment profiles. These profiles of protein families are useful tools for identifying conserved motifs, such as the catalytic triad of the serine protease family or the seven transmembrane helices of the G-protein coupled receptor family. Ultimately, the understanding of the critical motifs within a family is useful for identifying new members of the family. Due to the complexity of protein-ligand recognition, no universally accepted method exists for clustering small molecules into families with the same or similar biological activity. A combination of the concept of multiple sequence alignment and the 1-dimensional molecular representation described earlier offers a new method for profiling sets of small molecules with the same biological activity. These small molecule profiles can isolate key commonalities within the set of bioactive compounds much like a multiple sequence alignment can isolate critical motifs within a protein family. The small molecule profiles then make useful tools for searching small molecule databases for new compounds with the same biological activity. The technique is demonstrated here using the human ether-a-go-go potassium channel and the kinase SRC.Keywords
This publication has 30 references indexed in Scilit:
- Measuring Molecular Similarity and Diversity: Total Pharmacophore DiversityJournal of Medicinal Chemistry, 2001
- Crystal Structure of Hck in Complex with a Src Family–Selective Tyrosine Kinase InhibitorPublished by Elsevier ,1999
- Use of a Pharmacophore Model for the Design of EGFR Tyrosine Kinase Inhibitors: Isoflavones and 3-Phenyl-4(1H)-quinolonesJournal of Medicinal Chemistry, 1999
- FlexS: A Method for Fast Flexible Ligand SuperpositionJournal of Medicinal Chemistry, 1998
- Synthesis and Tyrosine Kinase Inhibitory Activity of a Series of 2-Amino-8H-pyrido[2,3-d]pyrimidines: Identification of Potent, Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase InhibitorsJournal of Medicinal Chemistry, 1998
- 2-Substituted Aminopyrido[2,3-d]pyrimidin-7(8H)-ones. Structure−Activity Relationships Against Selected Tyrosine Kinases and in Vitro and in Vivo Anticancer ActivityJournal of Medicinal Chemistry, 1998
- Development of a Binding Model to Protein Tyrosine Kinases for Substituted Pyrido[2,3-d]pyrimidine InhibitorsJournal of Medicinal Chemistry, 1998
- Structure−Activity Relationships for a Novel Series of Pyrido[2,3-d]pyrimidine Tyrosine Kinase InhibitorsJournal of Medicinal Chemistry, 1997
- Three‐dimensional, sequence order‐independent structural comparison of a serine protease against the crystallographic database reveals active site similarities: Potential implications to evolution and to protein foldingProtein Science, 1994
- Exhaustive Matching of the Entire Protein Sequence DatabaseScience, 1992