We will be making a regular point of providing you with the latest publications, reports and papers including developments and products from BioSolveIT and its associated owners.

Identification of novel inhibitors of bacterial surface enzyme Staphylococcus aureus Sortase A
Bala Chandra Chennaa, Bidhan A. Shinkrea, Jason R. Kinga, Aaron L. Luciusa, Sthanam V.L. Narayanab and Sadanandan E. Velu
Bioorg. Med. Chem. Lett., 18, 380–385, (2008)

A successful virtual screening approach of the bacterial surface enzyme Staphylococcus aureus Sortase A against ~150,000 compounds from the Maybridge and ChemBridge commercial compound libraries is reported. FlexX was used to identify novel inhibitors whilst activity was determined by monitoring of steady state cleavage of a model peptide substrate. Additional QSAR studies helped improve activity with the most active compound having an IC50 value of 58 µM in the fluorescence resonance energy transfer (FRET) enzymatic assays performed.
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Use of 3D QSAR Models for Database Screening: A Feasibility Study
Alexander Hillebrecht and Gerhard Klebe
J. Chem. Inf. Model., 48 (2), 384-96, (2008)

The paper reports on an automated protocol for aligning training and test set molecules for QSAR studies. FlexS was used to establish a reliable and robust method of consistent spatial alignment of molecules. The protocol was used to demonstrate that CoMFA and CoMSIA models based on this alignment protocol perform comparably well with similar models based on manually derived alignments using the protein’s binding pocket as a reference point along with subsequent force field relaxation. The study of QSAR methods showed that 3D QSAR models and the MACCS keys performed quite well with respect to affinity prediction. However, in terms of numerical affinity prediction the 3D QSAR models significantly outperformed the 1D and 2D approaches.
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Human Microsomal Prostaglandin E Synthase-1 (mPGES-1) Binding with Inhibitors and the Quantitative Structure-Activity Correlation
Mohamed D. M. AbdulHameed, Adel Hamza, Junjun Liu, Xiaoqin Huang and Chang-Guo Zhan
J. Chem. Inf. Model., 48 (1), 179-85, (2008)

The paper reports on molecular docking with FlexX and the application of 3D-QSAR methods to investigate inhibitor binding to a computational 3D structural model of Microsomal prostaglandin E synthase-1 (mPGES-1). All docked structures were found to be consistent with the generated 3D-QSAR contour maps. All of the results obtained from the 3D-QSAR analysis and molecular docking are qualitatively consistent with the experimental activity of the series of compounds investigated, suggesting that the binding modes determined by the molecular docking are correct. The study suggests that the generated 3D structural model of mPGES-1 is reasonable for further design of novel mPGES-1 inhibitors.
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SwiFT: an index structure for reduced graph descriptors in virtual screening and clustering
Robert Fischer and Matthias Rarey
J. Chem. Inf. Model., 47 (4), 1341-53, (2007)

The article reports on the implementation of a new indexing method for FTrees (SwiFT) for faster comparison of reduced graph descriptors like feature trees. The method reuses already computed partial results by indexing the subtrees of a compound data set with no loss in predictive accuracy. Screening of various datasets showed that SwiFT leads to a substantial reduction in run time for 1-n as well as for n-n and n-m comparisons. The study shows SwiFT to work well in a parallel computing environment and can handle searches without performing an n-n comparison. Due to implemented I/O routines and preprocessing steps which have to be done only once makes the method particularly applicable for Web services.
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