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ReCore: A Fast and Versatile Method for Scaffold Hopping Based on Small Molecule Crystal Structure Conformations
Patrick Maass, Tanja Schulz-Gasch, Martin Stahl, and Matthias Rarey
J. Chem. Inf. Model., 47 (2), 390 -399, (2007)

ReCore replaces central elements of known active structures to permit scaffold hopping into new chemical space. It enables exploration of large search spaces whilst avoiding structures with strained conformations in a quick interactive manner. A geometrical rank searching procedure is used with the ligand conformational crystal structure to identify compatible 3D fragments. Exit bond vector cuts are selected to define a core fragment for replacement. Additional pharmacophoric prioritization can be used to find fragments fulfilling all the applied constraints with results ordered by increasing deviation from the query constraints. The method was shown to propose new valid scaffold topologies for three different drug design scenarios relating to thyrotropin releasing hormone, HIV reverse transcriptase and HIV protease.
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ReCore
John H. Van Drie
J. Am. Chem. Soc., 131 (4), 1617, (2009)

The review states the origins of ReCore ensure that "the quality of the science underlying ReCore is first-rate". The JACS article also comments that "the way this software leads the user to think about the design of bioactive molecules is very appealing". ReCore was 'test driven' on 3 different systems for this review. The first was a problem encountered by the reviewer to discover novel D1-dopamine antagonist scaffolds using competitor compounds. ReCore produced the specific scaffold which led to Abbott's A-68930, an inhibitor which was designed in a pharma project. Other systems investigated were a peptide bound to a HIV protease and a pre-clinical candidate, in these experiments very interesting chemical suggestions were produced and the reviewer comments "ReCore did suggest some scaffolds that I had never thought of, which stimulated new thinking". The JACS article concludes that 'software of this sort belongs on the desk of any chemist designing bioactive molecules'.
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Structure-Based Rational Screening of Novel Hit Compounds with Structural Diversity for Cytochrome P450 Sterol 14α-Demethylase from Penicillium digitatum
Qingye Zhang, Ding Li, Pei Wei, Jie Zhang, Jian Wan, Yangliang Ren, Zhigang Chen, Deli Liu, Ziniu Yu, and Lingling Feng
J. Chem. Inf. Model., Publication Date (Web): January 20, 2010

The paper describes a virtual screening strategy for the identification of inhibitors for the cytorome P450 sterol 14α-demethylase (CYP51) which is a well known drug target for antifungal drugs. The CYP51 enzymes are involved essential sterol biosynthesis and integral membrane proteins, therefore homology models were used for SBDD. A pre-screening step of the ~114000 SPECs compound database was performed with Lipinksi's rules to yield ~79000 compounds. Further screening was undertaken with FlexX and FlexX-Pharm to identify 30 structurally diverse potential new inhibitors. Finally, bioaffinity testing revealed 7 new inhibitors that did not display the traditional azole-type molecular backbones but retained similar inhibitory activities to the commercial fungicide triadimefon.
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