Combination Assays and Molecular Docking can Identify Binding sites of Anti-Microtubule Drugs on Plasmodium falciparum Tubulin

Title:Combination Assays and Molecular Docking can Identify Binding sites of Anti-Microtubule Drugs on Plasmodium falciparum Tubulin

Volume: 16 Issue: 3

Author(s): Rimi Chakrabarti and Swati Patankar

Affiliation:

Keywords: Combination assays, molecular docking, Plasmodium falciparum, tubulin binding sites.

Abstract: Background: Lead compounds that target tubulin are being developed as agents against the human malaria parasite, Plasmodium falciparum. It is important to define the binding sites of these molecules on the tubulin dimer: Taxol, Vinca domains or novel binding pockets; however, extraction of native parasite tubulin is difficult.

Objective: This report aims to develop assays that allow the rapid assessment of binding sites of compounds on the tubulin dimer.

Method: We have developed a simple growth assay, using a combination of two anti-microtubule drugs that have overlapping binding sites, to study whether the two drugs act in synergistic, antagonistic or neutral manner. Additionally, Molecular docking was used to predict the binding sites of the drugs.

Results: The combination assay shows antagonistic interactions between drugs having overlapping binding sites. In contrast, drugs that do not bind to overlapping sites show no interactions or synergism in this combination assay. Molecular docking predictions show that indeed, drugs with antagonistic interactions in the growth assay do bind to overlapping sites.

Conclusion: These two assays can be a simple preliminary screen for the binding sites of novel anti-tubulin compounds being developed for malaria therapeutics.

Cite this article as:

Chakrabarti Rimi and Patankar Swati, Combination Assays and Molecular Docking can Identify Binding sites of Anti-Microtubule Drugs on Plasmodium falciparum Tubulin, Infectious Disorders - Drug Targets 2016; 16 (3) . https://dx.doi.org/10.2174/1871526516666160711164905