Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat. Rev. Drug Discov. 3, 935-949

Department of Computer-Aided Drug Discovery, Albany Molecular Research, Inc., 21 Corporate Circle, Albany, New York 12212-5098, USA.
Nature Reviews Drug Discovery (Impact Factor: 41.91). 12/2004; 3(11):935-49. DOI: 10.1038/nrd1549
Source: PubMed


Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.

Full-text preview

Available from:
  • Source
    • "In general terms, it is usually a problem of selection of predicted models that are closest to the native (real) complex out of a large set of diverse models. There are three kinds of scoring functions: physics-based [65], empirical [66], and knowledge-based [67]. The former two calculate binding energy as a sum of individual energy terms. "

  • Source
    • "The first one is an aaNAT product and shows that this enzyme holds a special place in the insect cuticle sclerotization [24] [25]. Molecular Docking studies allow us to analyze the orientation of the molecule (ligand/inhibitor), describing the affinity of a given molecule to a protein-binding site [26]. Virtual screening of chemicals is one of the main techniques currently used in Drug Discovery, testing natural and synthesized compounds [27] [28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Dengue is a Neglected tropical disease (NTDs) with high incidence in Brazil. This disease is caused by Dengue virus and is transmitted by Aedes aegypti mosquito. The search for new approaches for controlling of this disease is the subject of numerous studies. The aaNAT is a key enzyme in the metabolism of A. aegypti and is crucial in the sclerotization process, as well as regulation of circadian rhythm and inactivation of neurotransmitters. Computational techniques applied to studies of biological systems become an effective weapon in the mapping and manage- ment of 3D data structures, giving direction and guidance of potential ligands that can form stable complexes with targets of interest, using a Molecular Docking approach. The present study was conducted by a virtual screening, followed by docking calculations, in order to find molecules that could inhibit aaNAT. In this study, we used available compounds in SAM database (Bioinformatics and Medicinal Chemistry Laboratory—Southwest Bahia State University, Jequié-Bahia, Brazil), PubChem and ZINC. Results: The result of dockings with selected ligands showed good energy af- finities, presenting potential inhibitory interactions with the enzyme active site. Conclusions: The Coa-S-acetyl-tryptamine and 3-indoleacriloil-coenzyme-A showed the same binding energies −8.9 Kcal/Mol and were described as possible inhibitors of aaNAT.
    Computational Molecular Bioscience 09/2015; 5(1):35-44. DOI:10.4236/cmb.2015.53005
  • Source
    • "In the main, there are two aims of docking studies: accurate structural modeling and correct prediction of activity. However, the identification of molecular features that are responsible for specific biological recognition, or the prediction of compound modifications that improve potency, are them are much more focused on capturing energetic than entropic effects (Kitchen et al., 2004; Dash R, 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Developing a new agent in the anti-inflammatory and analgesic field, plants secondary metabolites can be a good source for the Non-Steroidal Anti-inflammatory Drugs (NSAID) drug development. For this purpose we subjected the active compounds of Mimosa pudica Linn. to reveal its potentiality by molecular docking analysis to find out its potent compound against COX which was done by GOLD docking analysis. Docking studies by GOLD showed that vitexin of Mimosa pudica had the highest fitness score against the COX-1 which is 60.43 and 63.49 for COX-2 enzyme. Vitexin of Mimosa pudica detected with significant fitness score and hydrogen bonding against COX-1 and COX-2 which may be a potent analgesic compound.
    Journal of Applied Pharmaceutical Science 08/2015; 5(07):71-75. DOI:10.7324/JAPS.2015.50712 · 0.47 Impact Factor
Show more