Data Mining Approaches for Compound Selection and Iterative Screening

Vogt, Martin; Bajorath, Jürgen

doi:10.1002/9780470567623.ch4

Cited by 4 publications

(3 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Virtual screening is the computational mirror image of the experimental high-throughput screening (HTS), , and it proved an efficient implementation in the drug design and discovery process. ,, Advances in computational and bioinformatics techniques and hardware solutions have allowed for fast mining of chemical and biological data to search for novel compounds with desired properties from commercial and private chemical databases , (see section for a discussion of available structural databases). , …”

Section: Enzyme–inhibitor Interactions: a Computational Point Of Viewmentioning

confidence: 99%

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

et al. 2013

View full text Add to dashboard Cite

Section: Enzyme–inhibitor Interactions: a Computational Point Of Viewmentioning

confidence: 99%

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

et al. 2013

View full text Add to dashboard Cite

“…Virtual screening has become a powerful tool in medicinal chemistry research and the drug discovery process. Various computational tools are available for mining of chemical and biological data to search for novel compounds with desired properties [Willett, ; Vogt and Bajorath, ; Heikamp and Bajorath, ]. Virtual screening approaches are either ligand [Bajorath, ; Stahura and Bajorath, ; Willett, ; Eckert and Bajorath, ; Heikamp and Bajorath, ] or structure based [Alperin et al., ; Bajorath, ; Jain, ; Kitchen et al., ; Shoichet, ; Klebe, ; Cheng et al., ; Heikamp and Bajorath, ].…”

Section: Introductionmentioning

confidence: 99%

A Hybrid Structure/Pharmacophore‐Based Virtual Screening Approach to Design Potential Leads: A Computer‐Aided Design of South African HIV‐1 Subtype C Protease Inhibitors

Soliman

2013

Drug Development Research

View full text Add to dashboard Cite

Preclinical Research Virtual screening is the computational mirror image of high‐throughput screening and refers to the in silico evaluation of the biological activity of different molecular entities. Various virtual screening strategies and workflows have been adopted to enhance the process of identification of potential hits. Structure‐based scoring relies solely on the interactions between the ligand and the target protein. Conversely, pharmacophore‐based scoring relies on the shape complementation of each ligand candidate to a three‐dimensional reference ligand. Herewith, we report a systematic integrated hybrid approach, along with the use of well‐defined physicochemical and biological filters, to enhance high‐ranking hit structures complementing the binding site architecture while also mimicking the three‐dimensional features of known active ligands. With a lack of experimental data on the South African HIV protease enzyme (C‐SA HIV PR), very limited research has been conducted to design inhibitors against this enzyme variant. In this paper, a focused integrated structure‐ and pharmacophore‐based virtual screening protocol is introduced to identify potential leads to assist toward designing potent inhibitors against the C‐SA PR variant. This rapid and systematic approach can potentially be implemented for the design and discovery of inhibitors against a wide range of biological targets.

show abstract

“…Virtual screening has become an important component of drug discovery and medicinal chemistry research. A wide range of computational methods are available for mining of chemical and biologic data to identify novel compounds with desired properties (1,2). In principle, virtual screening approaches are either ligand‐based (2–6) or target structure‐based (5–10).…”

mentioning

confidence: 99%

Computational Methodologies for Compound Database Searching that Utilize Experimental Protein–Ligand Interaction Information

Tan¹,

Batista²,

Bajorath³

2010

Chem Biol Drug Des

View full text Add to dashboard Cite

Ligand-and target structure-based methods are widely used in virtual screening, but there is currently no methodology available that fully integrates these different approaches. Herein, we provide an overview of various attempts that have been made to combine ligand-and structurebased computational screening methods. We then review different types of approaches that utilize protein-ligand interaction information for database screening and filtering. Interaction-based approaches make use of a variety of methodological concepts including pharmacophore modeling and direct or indirect encoding of protein-ligand interactions in fingerprint formats. These interaction-based methods have been successfully applied to tackle different tasks related to virtual screening including postprocessing of docking poses, prioritization of binding modes, selectivity analysis, or similarity searching. Furthermore, we discuss the recently developed interacting fragment approach that indirectly incorporates 3D interaction information into 2D similarity searching and bridges between ligand-and structurebased methods.Key words: fingerprints, interacting fragments, ligand-and structure-based virtual screening, pharmacophores, protein-ligand interactions, similarity searching, X-ray structures Virtual screening has become an important component of drug discovery and medicinal chemistry research. A wide range of computational methods are available for mining of chemical and biologic data to identify novel compounds with desired properties (1,2). In principle, virtual screening approaches are either ligand-based (2-6) or target structure-based (5-10). Small molecule-based methods typically rely on the concept of 'molecular similarity'. An important component of the molecular similarity concept is the Similarity Property Principle (11), which simply states similar molecules should have similar biologic activities. This principle provides the basis for whole-molecule similarity searching for which many different methods have been developed (2,4). Structure-based virtual screening (molecular docking) methods rely on the knowledge of 3D target structure and evaluate energetic and geometric criteria that determine small molecule binding (7-9). Ligand-and structure-based virtual screening approaches utilize different types of molecular information and are often complementary in nature. Accordingly, a number of efforts have been made to combine these approaches (12-18) and exploit their complementarity. Despite these efforts, fully integrated ligand-and structure-based virtual screening systems are yet to be developed. However, in fast-growing public domain databases abundant target and ligand information is becoming readily available. In particular, the Protein Data Bank (PDB) (19) offers the opportunity to explore many types of target-ligand interactions at the atomic level of detail based on complex crystal structures. Accordingly, exploring the wealth of currently available complex crystal structures and interaction information, a new genre of ...

show abstract

Data Mining Approaches for Compound Selection and Iterative Screening

Cited by 4 publications

References 82 publications

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

Integrated Approach to Structure-Based Enzymatic Drug Design: Molecular Modeling, Spectroscopy, and Experimental Bioactivity

A Hybrid Structure/Pharmacophore‐Based Virtual Screening Approach to Design Potential Leads: A Computer‐Aided Design of South African HIV‐1 Subtype C Protease Inhibitors

Computational Methodologies for Compound Database Searching that Utilize Experimental Protein–Ligand Interaction Information

Contact Info

Product

Resources

About