Cart
Article
Recore: A Fast and Versatile Method for Scaffold Hopping Based on Small Molecule Crystal Structure Conformations
Full Text HTML
Hi-Res PDFPurchase the full-text
- PDF/HTML,
figures/images,
references and tables,
(where available)
Section:Abstract
Replacing central elements of known active structures is a common procedure to enter new compound classes. Different computational methods have already been developed to help with this task, varying in the description of possible replacements, the query input, and the similarity measure used. In this paper, a novel approach for scaffold replacement and a corresponding software tool, called Recore, is introduced. In contrast to prior methods, our main objective was to combine the following three properties in one tool: to avoid structures with strained conformations, to enable the exploration of large search spaces, and to allow interactive use through short response times. We introduce a new technique employing 3D fragments generated by combinatorial enumeration of cuts. It allows focusing on fragments suitable for scaffold replacement while retaining conformational information of the corresponding crystal structures. Based on this idea, we present an algorithm utilizing a geometric rank searching approach. Given a geometric arrangement of two or three exit vectors and additional pharmacophore features, the algorithm finds fragments fulfilling all these constraints ordered by increasing deviation from the query constraints. For the validation of the approach, three different design scenarios have been used. The results obtained show that our approach is able to propose new valid scaffold topologies.
Citing Articles
Citation data is made available by participants in CrossRef's Cited-by Linking service. For a more comprehensive list of citations to this article, users are encouraged to perform a search in SciFinder.
This article has been cited by 12 ACS Journal articles (5 most recent appear below).
Pharmer: Efficient and Exact Pharmacophore Search
David Ryan Koes and Carlos J. CamachoJournal of Chemical Information and Modeling2011 Article ASAPPharmer: Efficient and Exact Pharmacophore Search
David Ryan Koes and Carlos J. CamachoJournal of Chemical Information and Modeling2011 Article ASAPPharmacophore search is a key component of many drug discovery efforts. Pharmer is a new computational approach to pharmacophore search that scales with the breadth and complexity of the query, not the size of the compound library being screened. Two ...
Overview: Fragment-Based Drug Design
Rachelle J. Bienstock2011 (), 1-26Overview: Fragment-Based Drug Design
Rachelle J. Bienstock2011 (), 1-26Fragment-based drug design has recently risen to great prominence as a new methodology for novel lead identification. This chapter is a general overview of computational methods for all three phases of fragment-based ligand design: (1) Designing and ...
From Structure Diagrams to Visual Chemical Patterns
Karen Schomburg, Hans-Christian Ehrlich, Katrin Stierand, and Matthias RareyJournal of Chemical Information and Modeling2010 50 (9), 1529-1535From Structure Diagrams to Visual Chemical Patterns
Karen Schomburg, Hans-Christian Ehrlich, Katrin Stierand, and Matthias RareyJournal of Chemical Information and Modeling2010 50 (9), 1529-1535The intuitive way of chemists to communicate molecules is via two-dimensional structure diagrams. The straightforward visual representations are mostly preferred to the often complicated systematic chemical names. For chemical patterns, however, no ...
MORPH: A New Tool for Ligand Design
Brett R. Beno and David R. LangleyJournal of Chemical Information and Modeling2010 50 (6), 1159-1164MORPH: A New Tool for Ligand Design
Brett R. Beno and David R. LangleyJournal of Chemical Information and Modeling2010 50 (6), 1159-1164A frequently employed strategy in drug discovery efforts is to replace aromatic rings in known active compounds with alternative aromatic moieties to create novel compounds with improved potency and/or adsorption, distribution, metabolism, excretion, and ...
Molecular Shape and Medicinal Chemistry: A Perspective
Anthony Nicholls, Georgia B. McGaughey, Robert P. Sheridan, Andrew C. Good, Gregory Warren, Magali Mathieu, Steven W. Muchmore, Scott P. Brown, J. Andrew Grant, James A. Haigh, Neysa Nevins, Ajay N. Jain and Brian KelleyJournal of Medicinal Chemistry2010 53 (10), 3862-3886Molecular Shape and Medicinal Chemistry: A Perspective
Anthony Nicholls, Georgia B. McGaughey, Robert P. Sheridan, Andrew C. Good, Gregory Warren, Magali Mathieu, Steven W. Muchmore, Scott P. Brown, J. Andrew Grant, James A. Haigh, Neysa Nevins, Ajay N. Jain and Brian KelleyJournal of Medicinal Chemistry2010 53 (10), 3862-3886
Tools
-
Add to Favorites
-
Download Citation
-
Email a Colleague -
Permalink
Order Reprints
Rights & Permissions
Citation Alerts
Accession Codes
History
- Published In Issue March 26, 2007
- Received March 16, 2006
ACS
Network
Facebook
Tweet This
CiteULike
Newsvine
Digg This
Delicious
