Close
Help
Need Help?





JOURNAL

Bioinformatics and Biology Insights

365,181 Journal Article Views | Journal Analytics

Computational Design of Targeted Inhibitors of Polo-Like Kinase 1 (Plk1)

Submit a Paper



Publication Date: 20 Feb 2012

Type: Original Research

Journal: Bioinformatics and Biology Insights

Citation: Bioinformatics and Biology Insights 2012:6 23-31

doi: 10.4137/BBI.S8971

Abstract

Computational design of small molecule putative inhibitors of Polo-like kinase 1 (Plk1) is presented. Plk1, which regulates the cell cycle, is often over expressed in cancers. Down regulation of Plk1 has been shown to inhibit tumor progression. Most kinase inhibitors interact with the ATP binding site on Plk1, which is highly conserved. This makes the development of Plk1-specific inhibitors challenging, since different kinases have similar ATP sites. However, Plk1 also contains a unique region called the polo-box domain (PBD), which is absent from other kinases. In this study, the PBD site was used as a target for designed Plk1 putative inhibitors. Common structural features of several experimentally known Plk1 ligands were first identified. The findings were used to design small molecules that specifically bonded Plk1. Drug likeness and possible toxicities of the molecules were investigated. Molecules with no implied toxicities and optimal drug likeness values were used for docking studies. Several molecules were identified that made stable complexes only with Plk1 and LYN kinases, but not with other kinases. One molecule was found to bind exclusively the PBD site of Plk1. Possible utilization of the designed molecules in drugs against cancers with over expressed Plk1 is discussed.


Downloads

PDF  (985.49 KB PDF FORMAT)

RIS citation   (ENDNOTE, REFERENCE MANAGER, PROCITE, REFWORKS)

BibTex citation   (BIBDESK, LATEX)

XML

PMC HTML


Sharing


Our Service Promise

  • Prompt Processing (3 Weeks to Editorial Decision)
  • Fair, Independent Peer Review
  • High Visibility & Extensive Indexing
What Your Colleagues Say About Bioinformatics and Biology Insights
Bioinformatics and Biology Insights helps to reach all people with the latest results on research which directly helps them and with their needs. Three of our co-authors are from Burkina Faso, the malaria holoendemic region our research is based on, and serving as motivation for all our efforts for better treatment of malaria.  It is good to be social and it is good to promote science world-wide through open access.
Dr Thomas Dandekar (University of Wurzburg, European Molecular Biology Laboratory, Heidelberg, Germany)
More Testimonials

Quick Links




Follow Us We make it easy to find new research papers.
Email Alerts RSS Feeds
Facebook Google+ Twitter
Pinterest Tumblr YouTube




SUBJECT HUBS
Author Survey Results
author_survey_results
All authors are surveyed after their articles are published. Authors are asked to rate their experience in a variety of areas, and their responses help us to monitor our performance. Presented here are their responses in some key areas. No 'poor' or 'very poor' responses were received; these are represented in the 'other' category.
See Our Results