ACAD107835

A postdoctoral research position is available in the group of Prof. Adrian Mulholland as part of the European Research Council (ERC) Advanced Project PREDACTED (Predictive computational models for Enzyme Dynamics, Antimicrobial resistance, Catalysis and Thermoadaptation for Evolution and Design, https://cordis.europa.eu/project/id/101021207). This project involves the application of computational chemistry and molecular simulation methods to investigate enzymes involved in antibiotic resistance. This project uses molecular simulations to investigate how enzymes function, how they achieve their catalytic power, how they are inhibited (including allosteric inhibition and regulation), how they adapt to different environmental conditions and how they evolve (e.g. to develop new activities). Researchers will develop simulation models that can predict enzyme dynamics and the changes associated with catalysis. This will address important challenges associated with antibiotic resistance. This
project is based in the Centre for Computational Chemistry, School of Chemistry, University of Bristol. The School of Chemistry is ranked first in the UK in the latest Research Excellence Framework (Times Higher Education analysis of REF2021).

What will you be doing?

You will apply molecular simulation methods to model enzyme-catalysed reaction mechanisms and protein dynamics. You will build models of enzyme complexes and test effects of physical conditions. You will apply multiscale methods to model reactions in enzymes, and identify mechanisms. You will compare binding and reaction of different substrates. You will model reaction intermediates and simulate effects of protein dynamics on reaction. You will compare the results with theoretical predictions to test models and theories of enzyme catalysis and evolution. You will analyse effects of mutations, contribute to protein and inhibitor design and to the interpretation of experimental data. You will work closely with experimental biochemists and structural biologists in engineering proteins and in designing and interpreting experiments.

You are a highly motivated computational molecular scientist looking to take the next step in your research career by joining a leading research group, and to collaborate closely with experiments. This position would suit a skilled researcher with a PhD in Chemistry, Biochemistry or related field and expertise in computational chemistry or working towards one. Experience of molecular dynamics simulations, multiscale simulation, and modelling enzyme catalytic mechanisms, and knowledge of structural biology, are essential. This project will provide excellent experience of simulation methods and advanced computing, and the opportunity to work closely with experimental groups on antibiotic resistance.