A Practical Perspective : The Effect of Ligand Conformers on the Negative Image-Based Screening
Ahinko, M., Kurkinen, S., Niinivehmas, S., Pentikäinen, O., & Postila, P. (2019). A Practical Perspective : The Effect of Ligand Conformers on the Negative Image-Based Screening. International Journal of Molecular Sciences, 20(11), Article 2779. https://doi.org/10.3390/ijms20112779
Published inInternational Journal of Molecular Sciences
© 2019 by the authors.
Negative image-based (NIB) screening is a rigid molecular docking methodology that can also be employed in docking rescoring. During the NIB screening, a negative image is generated based on the target protein’s ligand-binding cavity by inverting its shape and electrostatics. The resulting NIB model is a drug-like entity or pseudo-ligand that is compared directly against ligand 3D conformers, as is done with a template compound in the ligand-based screening. This cavity-based rigid docking has been demonstrated to work with genuine drug targets in both benchmark testing and drug candidate/lead discovery. Firstly, the study explores in-depth the applicability of different ligand 3D conformer generation software for acquiring the best NIB screening results using cyclooxygenase-2 (COX-2) as the example system. Secondly, the entire NIB workflow from the protein structure preparation, model build-up, and ligand conformer generation to the similarity comparison is performed for COX-2. Accordingly, hands-on instructions are provided on how to employ the NIB methodology from start to finish, both with the rigid docking and docking rescoring using noncommercial software. The practical aspects of the NIB methodology, especially the effect of ligand conformers, are discussed thoroughly, thus, making the methodology accessible for new users. ...
Publication in research information system
MetadataShow full item record
Showing items with similar title or keywords.
Virtanen, Salla (University of Jyväskylä, 2013)
Niinivehmas, Sanna (University of Jyväskylä, 2015)
Rauhamäki, Sanna; Postila, Pekka; Niinivehmas, Sanna; Kortet, Sami; Schildt, Emmi; Pasanen, Mira; Manivannan, Elangovan; Ahinko, Mira; Koskimies, Pasi; Nyberg, Niina; Huuskonen, Pasi; Multamäki, Elina; Pasanen, Markku; Juvonen, Risto O.; Raunio, Hannu; Huuskonen, Juhani; Pentikäinen, Olli (Frontiers Media S.A., 2018)Monoamine oxidase B (MAO-B) catalyzes deamination of monoamines such as neurotransmitters dopamine and norepinephrine. Accordingly, small-molecule MAO-B inhibitors potentially alleviate the symptoms of dopamine-linked ...
Ylilauri, Mikko (University of Jyväskylä, 2014)
Structural analysis of two foldamer-type oligoamides – the effect of hydrogen bonding on solvate formation, crystal structures and molecular conformation Suhonen, Aku; Nauha, Elisa; Salorinne, Kirsi; Helttunen, Kaisa; Nissinen, Maija (RSC Publishing, 2012)The crystal structures and molecular conformations of two foldamer-type oligoamides were analyzed. One polymorphic form and seven solvates were found for N¹,N³-bis(2-benzamidophenyl)benzene-1,3-dicarboxamide (the benzene ...