Docking and scoring in virtual screening for drug discovery: Methods and applications

Department of Computer-Aided Drug Discovery, Albany Molecular Research, Inc., 21 Corporate Circle, Albany, New York 12212-5098, USA.
dressNature Reviews Drug Discovery (Impact Factor: 37.23). 12/2004; 3(11):935-49. DOI: 10.1038/nrd1549
Source: PubMed

ABSTRACT 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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the current study it was found that dieckol isolated from edible brown algae, Ecklonia cava (EC), as potent anti-proliferative and anti-angiogenic agent. Vascular endothelial growth factor (VEGF) induced EA.hy926 cell proliferation was suppressed by dieckol treatment. Further, it showed a significant inhibition of cell migration via inhibiting the protein and gene expression levels of matrix metalloproteinases, MMP-2 and -9. The signaling cascade underlying these responses was found as the dieckol induced inhibition of mitogen-activated protein kinase (MAPK) signaling pathway molecules, ERK and p38. Docking calculations were carried out on AP-N, VEGFR-1, MMP-2, MMP-9, Akt and Erk2 proteins model. Collectively, these results demonstrate the effective anti-proliferative and anti-migratory activity of dieckol on VEGF induced EA.hy926 through MAPK molecular signaling pathways which could be effectively correlated to its potential as an anti-angiogenic candidate. Therefore, this study reveals the potential of dieckol to be used in the design of anti-angiogenic agents.
    Environmental Toxicology and Pharmacology 01/2015; 39(1). DOI:10.1016/j.etap.2014.11.027 · 1.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Molecular Modeling is essential tool in the drug design process describes the generation, manipulation or representation of 3D structures of the molecules and associated physico-chemical properties while docking predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. A cold active lipase producing potential psychrophilic bacteria (GN) was isolated and identified by 16S rRNA molecular studies as Pseudomonas vancouverensis. Lipase gene from closely related species P. fluorescens was investigated for their functional role and in silico characterization using molecular modeling and docking studies. A 3D structure of lipase gene was generated with SWISS-MODEL and Discovery Studio 3.0. The stereochemistry of the constructed model of cold active lipase was subjected to energy minimization and the stereo-chemical quality of the predicted structure was assessed. The superimposition of the template (PDBID: 2Z8X) with predicted structure showed that weighted root mean square deviation of Cα trace between the template and the final refined model was 0.2 Å with a significant Zscore of 8.2 and sequence identity was 80.5%. Three ligands P-Nitrophenol, Acetate ion and Diethyl phosphonate were taken for docking calculation with generated structure. They were interacting on the functional motifs of predicted model. It has been observed that Leu26, Tyr29, Asn31, Asp33, Pro315 and Thr316 residues were involved in hydrogen bonding interactions with selected ligands. So these interacted residues can be used as prominent active binding sites and which was common to the predicted active site. Based on above investigations it has been found that P. vancouverensis lipase protein can play a similar role in lipid metabolic process and triglyceride lipase functional activity as reported for P. fluorescens lipase protein.
    International Journal of Applied Biology and Pharmaceutical Technology 01/2015; 6(1):59-66. · 0.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The field of structural bioinformatics and computational biophysics has undergone a revolution in the last 10 years. Developments that are captured annually through the 3DSIG meeting, upon which this article reflects. An increase in the accessible data, computational resources and methodology has resulted in an increase in the size and resolution of studied systems and the complexity of the questions amenable to research. Concomitantly, the parameterization and efficiency of the methods have markedly improved along with their cross-validation with other computational and experimental results. The field exhibits an ever-increasing integration with biochemistry, biophysics and other disciplines. In this article, we discuss recent achievements along with current challenges within the field. © The Author 2014. Published by Oxford University Press.
    Bioinformatics 12/2014; DOI:10.1093/bioinformatics/btu769 · 4.62 Impact Factor


Available from

Similar Publications