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"Locking the lock": design of interleukin 10 inhibiting biomolecules by a structure-based molecular dynamics simulation approach
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"Locking the lock": design of interleukin 10 inhibiting biomolecules by a structure-based molecular dynamics simulation approach

Tianfang Wang
USC Research Conference, 2014 (Sunshine Coast, Australia, 14-Jul-2014–18-Jul-2014)
University of the Sunshine Coast
2014
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Abstract

Clinical Sciences
Interleukin 10 (IL10) is a cytokine with pleiotropic effects in immune-regulation and inflammation. Remarkable over-expression of IL10 has been found in the plasma of patients with chronic viral infections and cancers, which can diminish immune responses and result in serious consequences. Blockage of IL10 receptor from binding IL10 by particular molecule(s) has recently been considered as a feasible way to solve this problem. However, very few clinically useful molecules have been found suitable for this aim, and clinical grade monoclonal antibodies are difficult to produce due to high production cost and complex regulatory approval process. This project used high-level computational simulations to design macromolecules that can act as IL10 inhibitors in vitro, and in addition possess the advantages of ease of production and regulatory approval. The aims of this project are:- (i) design macromolecules that have the ability to block the signalling process between IL10 and its receptor in silico (Aim 1); (ii) test designed macromolecules for inhibiting IL10's biological function (Aim 2); (iii) based on bioassay results obtained from Aim 2, we will revisit computational design (modelling stage-II) of macromolecules, whereby macromolecule structure will be modified and improved, to obtain more active, less cytotoxic and low production cost macromolecules (Aim 3). This research was carried out by Dr Tianfang Wang and Dr Xiaosong Liu, under the support of a USC/SCC grant.

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