Three-Dimensional Pharmacophore Methods in Drug Discovery

Virtual Screening Strategies in Drug Design

“…Através da sobreposição dos compostos ativos, por exemplo, é possível criar um esboço das principais características compartilhadas entre as moléculas no espaço tridimensional, como possíveis grupos capazes de realizar ligações de hidrogênio, bem como grupos hidrofóbicos, com carga positiva ou negativa. [94][95][96] Inicialmente, a triagem virtual baseada em ligantes foi desenvolvida a partir de descritores 2D ou características moleculares espe ífi as fi ge p i ts de i adas da estrutura de compostos ativos de referência e comparados com os correspondentes descritores das moléculas das bases de dados, lançando mão de uma medida de similaridade, como por exemplo o famoso coeficiente de Tanimoto. Os elementos farmacofóricos chaves em uma busca podem ser: um grupo específico de átomos, uma região molecular volumosa, grupamentos doadores e aceptores de ligação de hidrogênio, grupamentos com cargas, hidrofóbicos e/ou anéis aromáticos, associados a restrições geométricas incluindo distâncias e ângulos de ligação.…”

Chemoinformatics at the University of Sheffield 2002–2014

“…Pharmacophore mapping is the process of determining a pharmacophore and can be structure-based or ligand-based. [61][62] In structure-based methods, the three-dimensional structure of the binding site is used to suggest locations for complementary features in a small molecule. Ligand-based methods are used when the three dimensional structure of the target is unknown and an attempt is made to elucidate the requirements for binding from a series of known active molecules.…”

Receptor Chemoprint Derived Pharmacophore Model for Development of CAIX Inhibitors

“…Advancements in computational techniques [8][9][10] played a vital role in High Throughput Screening (HTS) to design new chemical entities [11,12]. Pharmacophore modelling, Quantitative Structure Activity Relationship (QSAR), virtual screening, docking simulation and pharmacokinetics based analyses are used for development of new chemical entities [10,13].…”

“…Pharmacophore modelling, Quantitative Structure Activity Relationship (QSAR), virtual screening, docking simulation and pharmacokinetics based analyses are used for development of new chemical entities [10,13]. However, the ligand based pharmacophore models are significantly depend on selected training set and conformation generation method [14].…”

“…In the present study, docking simulations are carried out by various sets of experimentally known CAIX inhibitors, and interacting active site residues were sorted accordingly to pharmacophore features with LigandScout 3.1 [21]. Virtual screening was found to be a successful method especially when combined with molecular docking studies [10]. The predicted pharmacophore has been employed in virtual screening with a ZINC database to identify a plausible potent lead for CAIX inhibitor.…”