A1 Refereed original research article in a scientific journal
A Practical Perspective: The Effect of Ligand Conformers on the Negative Image-Based Screening
Authors: Ahinko M, Kurkinen ST, Niinivehmas SP, Pentikäinen OT, Postila PA
Publisher: MDPI
Publication year: 2019
Journal: International Journal of Molecular Sciences
Journal name in source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Journal acronym: INT J MOL SCI
Article number: 2779
Volume: 20
Issue: 11
Number of pages: 25
ISSN: 1422-0067
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms20112779
Web address : https://www.mdpi.com/1422-0067/20/11/2779/htm
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/41309797
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.
Downloadable publication This is an electronic reprint of the original article. |  |
