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An extended reduced graph approach (ErG) is presented that uses pharmacophore-type node descriptions to encode the relevant molecular properties. The basic idea of the method can be described as a hybrid approach of reduced graphs (Gillet et al. J. Chem. Inf. Comput. Sci. 2003, 43, 338-345) and binding property pairs (Kearsley et al. J. Chem. Inf. Comput.(More)
Although orphan drug applications required by the EMEA must include assessments of similarity to pre-existing products, these can be difficult to quantify. Here we illustrate a paradigm in comparing nilotinib to the prototype kinase inhibitor imatinib, and equate the degree of structural similarity to differences in properties. Nilotinib was discovered(More)
The coronavirus main protease, M(pro), is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential M(pro) inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective(More)
Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and(More)
For three target proteins with different binding pocket characteristics (size and shape, hydrophobicity, hydrogen-bonding) a structure-based validation of the translationally and rotationally invariant 3D-QSAR technique MaP is performed (MaP: Mapping Property distributions of molecular surfaces). The structure-based validation procedure comprises two steps:(More)
The coronavirus main protease, M(pro), is considered a major target for drugs suitable to combat coronavirus infections including the severe acute respiratory syndrome (SARS). In this study, comprehensive HPLC- and FRET-substrate-based screenings of various electrophilic compounds were performed to identify potential M(pro) inhibitors. The data revealed(More)
A novel series of acetylcholinesterase (AChE) inhibitors of the bispyridinium type was synthesized and the inhibitory activity against AChE and butyrylcholinesterase (BChE) measured. In essence, the substitution pattern influenced the inhibitory potency against AChE, where the most active bispyridiniumoxime (TMB-4) was bisbenzyl substituted followed by(More)
Variable selection is applied frequently in QSAR research. Since the selection process influences the characteristics of the finally chosen model, thorough validation of the selection technique is very important. Here, a validation protocol is presented briefly and two of the tools which are part of this protocol are introduced in more detail. The first(More)
A novel molecular descriptor called MaP (mapping property distributions of molecular surfaces) is presented. It combines facile computation, translational and rotational invariance, and straightforward interpretability of the computed models. A three-step procedure is used to compute the MaP descriptor. First, an approximation to the molecular surface with(More)
A general purpose force field such as MMFF94/MMFF94s, which can properly deal with a wide range of diverse structures, is very valuable in the context of a cheminformatics toolkit. Herein we present an open-source implementation of this force field within the RDKit. The new MMFF functionality can be accessed through a C++/C#/Python/Java application(More)