Redesigning protein dynamics

In this project, we will develop and apply a novel approach to design protein dynamics based on cycles of computer predictions and experiments in the lab.

Synthetic biology is aimed at introducing changes in organisms to redesign their biological functions. For example, building new materials from nano-scale bacterial fibres. Most biological functions are performed by proteins, which are like small machines with moving parts. However, unlike an engine, their shape constantly changes through a process called dynamics. As this is integral to how proteins work, the most desirable way to modify protein function would be to change how they move. In this project, we will develop and apply a novel approach to design protein dynamics based on cycles of computer predictions and experiments in the lab. 

The outcome of this project will be the first-ever strategy to make targeted changes to a protein function by redesigning how it moves and changes shape. Using a unique combination of computational and experimental techniques, it will be possible to redesign the function of a protein in a few months. This will for example provide fine-tuned control of enzymatic catalysis.

Meet the Principal Investigator(s) for the project

Dr Alessandro Pandini - My research activity focuses on the development and application of computational methods to study protein dynamics and its role in protein-ligand binding, protein-protein interactions, and protein design. I obtained my PhD in Computational Chemistry at the University of Milan-Bicocca under the supervision of Prof. Laura Bonati. As part of her research group I contributed to the unveil the molecular mechanism of toxic response mediated by binding of dioxins to the Aryl hydrocarbon Receptor. In 2008 I was awarded a Marie Curie Inter European Fellowship to work at the MRC National Institute for Medical Research (NIMR) under the supervision of Dr. Willie R. Taylor and Dr. Jens Kleinjung. From 2011 to 2014 he was a BBSRC-funded postdoctoral research assistant in the group of Prof. Franca Fraternali at King’s College London working on methods to investigate allosteric regulation, and to analyse protein-protein interaction interfaces and networks. During my career I developed and applied novel approaches combining structural bioinformatics and molecular simulation to address challenging biological questions, especially in relation to protein function, allosteric regulation and drug design. I introduced novel points of view in the definition of the limits and potential of molecular docking on theoretical models and in the use of molecular dynamics for drug design and medicinal chemistry. In particular, I developed an innovative computational method to detect local functional motions and to describe allosteric transmission in protein structures. Most recently, in collaboration with Dr. Arianna Fornili (QMUL), I contributed to the development of a novel strategy for biasing the sampling of local states to drive the global conformational transitions in proteins. In collaboration with Dr. Shahid Khan (LBNL – Berkeley Lab) and Dr. Willie Taylor, I have contributed to explain the relationships between residue coevolution and molecular dynamics in two bacterial ring assemblies. 

Project last modified 21/11/2023