Periodic Reporting for period 1 - ASSEMBLY (Advancing Synthethic Supramolecular chemical biology)
Reporting period: 2019-08-01 to 2021-07-31
To start to tackle these issues a better understanding signaling networks is required. Split proteins offer great advantages when designing supramolecular synthetic signalling networks. When combined with our cucurbituril-bases molecular recognition system they have great promise to function in parallel with any natural signalling systems, thus having the potential to limit its biological interference, while still effecting the desired interactions.
The formed supramolecular assembly between the cucurbituril and its guests can be modulated via competitor systems. The development of a light-sensitive peptidic inhibitor allows for the direct assembly of the splitprotein-cucurbituril complex in the aqueous media. Additionally a light-sensitive peptidic inhibitor was developed that, after being exposed to light facilitated the direct, irreversible de-assembly of the reformed splitprotein-cucurbituril complex in aqueous media.
To increase the understanding of the multi-complex equilibria that are formed in the model systems, the use of computational modeling proved valuable. However, as every system is different it was found time-consuming to have to develop and mathematically derive all the elaborate thermodynamic equations by hand. To facilitate this, the error prone method was replaced by an automated derivitization process. The model builder program was designed to be easy to use and modular. Stress tests show that the novel developed algorithm can cope with very large multi-component complexes with ease.
The manuscript detailing the novel approach to construct computational models based on multi-component complex equilibria is currently under review. The program is already been shared and tested by different research groups within the department and has been useful in the creation of several models. The developed models help provide key insights into the molecular mechanisms that are underlying many of the processes that are studied in the department. As soon as the project clear review and the full program and coding will be publicly available.