Combined Virtual Screening Strategies

Alan      Talevi; Luciana      Gavernet; Luis   E.   Bruno-Blanch

Abstract

The progress in chemical knowledge and synthetic technologies over the last fifty-years has dramatically increased the synthetic accessible chemical entities. Exploration of natural products rich chemodiversity has also expanded the vast chemical universe where medicinal chemist can pursue the identification of new therapeutic agents. Virtual Screening (VS) benefits from computational technology to explore the increasingly vast chemical universe in an efficient manner. The different VS approaches may be characterized by the computational and human time they require, from the highly automated and fast 2D-QSAR ligand-based VS to the more demanding 3D QSAR and target-based (docking) methodologies. Recently, several studies based on the integration of different VS approaches have been proposed, demonstrating that the hit recovery rate may be maintained (or even increased) with a substantial reduction of computing times. Combined virtual screening methodologies usually begin with the least-demanding approaches at the beginning of the VS process and progress to the more accurate, time consuming techniques in the last stages. This review discusses recent 2D/3D QSAR and ligand-based/target-based “synergistic” combinations that allow speeding-up the VS process, permitting accurate and efficient studies on large databases. The impact of the combination of different techniques on the chemical diversity of the compounds retrieved is also discussed.

Keywords: Combined virtual screening, docking, ligand based methodologies, QSAR, pharmacophore

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