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Demystifying P2Y1 Receptor Ligand Recognition through Docking and Molecular Dynamics Analyses

10.1021/acs.jcim.7b00528

2017-11-28

We performed a molecular modeling analysis of 100 nucleotide-like bisphosphates and 46 non-nucleotide arylurea derivatives previously reported as P2Y1R binders using the recently solved hP2Y1R structures. We initially docked the compounds at the X-ray structu...

Macrocycle Conformational Sampling by DFT-D3/COSMO-RS Methodology

10.1021/acs.jcim.7b00453

2017-11-28

To find and calibrate a robust and reliable computational protocol for mapping conformational space of medium-sized molecules, exhaustive conformational sampling has been carried out for the series of seven macrocyclic compounds of varying ring size and one a...

Coupling Matched Molecular Pairs with Machine Learning for Virtual Compound Optimization

10.1021/acs.jcim.7b00298

2017-11-27

Matched molecular pair (MMP) analyses are widely used in compound optimization projects to gain insights into structure–activity relationships (SAR). The analysis is traditionally done via statistical methods but can also be employed together with machine lea...

xMaP – An interpretable alignment-free 4D-QSAR technique based on molecular surface properties and conformer ensembles

10.1021/acs.jcim.7b00419

2017-11-27

A novel alignment-free molecular descriptor called xMaP (flexible MaP descriptor) is introduced. The descriptor is the advancement of the previously published translationally and rotationally invariant 3D descriptor MaP (Mapping Property distributions onto th...

Differential Compound Prioritization via Bi-Directional Selectivity Push with Power

10.1021/acs.jcim.7b00552

2017-11-27

Effective in silico compound prioritization is a critical step to identify promising drug candidates in the early stages of drug discovery. Current computational methods for compound prioritization usually focus on ranking the compounds based on one property,...

Identification of Allosteric Modulators of Metabotropic Glutamate 7 Receptor Using Proteochemometric Modeling

10.1021/acs.jcim.7b00338

2017-11-26

Proteochemometric modeling (PCM) is a computational approach that can be considered an extension of quantitative structure-activity relationship (QSAR) modeling, where a single model incorporates information for a family of targets and all the associated liga...

NP-StructurePredictor: Prediction of Unknown Natural Products in Plant Mixtures

10.1021/acs.jcim.7b00565

2017-11-22

Identification of the individual chemical constituents of a mixture, especially solutions extracted from medicinal plants, is a time-consuming task. The identification results are often limited by challenges such as the development of separation methods and t...

Identification of Protein–Ligand Binding Sites by Sequence Information and Ensemble Classifier

10.1021/acs.jcim.7b00307

2017-11-21

Identifying protein–ligand binding sites is an important process in drug discovery and structure-based drug design. Detecting protein–ligand binding sites is expensive and time-consuming by traditional experimental methods. Hence, computational approaches pro...

Patterns of Ligands Coordinated to Metallocofactors Extracted from the Protein Data Bank

10.1021/acs.jcim.7b00468

2017-11-21

A new R tool is described that rapidly identifies, ranks, and clusters sequence patterns coordinated to metallocofactors. This tool, PdPDB, fills a void because, unlike currently available tools, PdPDB searches through sequences with metal coordination as the...

Expanding the Armory: Predicting and Tuning Covalent Warhead Reactivity

10.1021/acs.jcim.7b00553

2017-11-21

Targeted covalent inhibition is an established approach for increasing the potency and selectivity of potential drug candidates, as well as identifying potent and selective tool compounds for target validation studies. It is evident that identification of rev...