Background:

The Hay group are interested in how biological processes – reactions and interactions – are governed by their underlying physics/physical chemistry. The main focus of this work is the role of protein dynamics and quantum mechanics during enzyme catalysis and the use of proteins and enzymes as structural and/or functional biomaterials and sensors. This work employs both experimental and theoretical approaches, with an emphasis on instrument and method development and the development of new theory and models to underpin experiment. Much of the work involves computational chemistry, often combing molecular dynamics (MD) simulations with enzyme active site density functional theory (DFT) ‘cluster’ models.

Sam received a first class honours degree in biochemistry from the University of Otago, New Zealand (2000), and his PhD in biophysics from the Australian National University (2004). He then spent a year at Stockholm University as a Wenner-Gren visiting postdoctoral fellow (2004-2005) before moving to the University of Manchester to work with Nigel Scrutton as a postdoctoral research associate. Sam was a recipient of the RSC Rita and John Cornforth Award in 2009 and in 2010 he received a BBSRC David Phillips fellowship. In 2014 he was made a lecturer, in 2017 senior lecturer, in 2019 reader and in 2021 he became Professor of Biophysical Chemistry.

In silico enzymology

We use a range of computational chemistry, machine learning and bio/cheminformatics approaches to study a range of (bio)chemical systems, with a major focus on enzymes. Molecular dynamics in combination with homology modelling and molecular docking can generate (literally) working models of proteins, which are difficult or impossible to crystallise. Ab initio and DFT methods are used to model enzyme active sites, study enzyme chemistry, and augment X-ray crystallography studies, e.g. when characterising new cofactors.

The role of quantum mechanics in biological processes

While the physical laws underpinning biochemistry and enzymology are generally classical (Newtonian) in nature, we have shown that quantum mechanical tunnelling can play a major role in enzymatic hydrogen transfer reactions. We are now interested in how ubiquitous this phenomenon is, and whether room temperature tunnelling is also a feature of heavy atom rearrangement and transfer during catalysis. We are also interested in whether enzymes actively exploit tunnelling by coupling environmental dynamics to the reaction coordinate, effectively compressing the reaction barrier. A major focus of our work is the development of models that can ‘join the dots’ between the computational and experimental approaches that are jointly used to study these reactions.

Kinetic models of complex reactions

Much of enzymology hinges on the interpretation of measured rate constants of e.g. enzyme-catalysed turnover. These rate constants are usually extracted from steady-state enzyme assays or from pre-steady state approaches such as stopped-flow spectrometry. Unfortunately, these approaches often only allow the measurements of observed (phenomenological) rate constants. We are interested in developing methods that use numerical modelling and global analysis of kinetic data to extract the microscopic rate constants needed to build kinetic models of complex enzymatic reaction mechanisms.

EPR and high pressure spectroscopy

I used to manage the EPR facillity in the MIB, and a focus of our group is combining computational chemistry with EPR distance (PELDOR/DEER) measurements as a hybrid structural biology approach.

Also, In collaboration with the Scrutton, Waltho and Phillips groups, we are developing high pressure methods of experimentally probing structural and mechanistic aspects of protein and enzyme function. Experimentally, these include stopped-flow, NMR and fluorescence lifetime-based approaches, while we combine these with high pressure molecular dynamics simulations and kinetic modelling.

We recruit from a wide range of backgrounds, including biochemistry, chemistry, physics, engineering, applied mathematics and computer science.

We are always interested in talking to self-funded students and prospective postdoctoral/visiting researchers and can tailor projects to your interests and strengths - i.e. 'dry' (theoretical/computational), 'damp' (mixed theory and experiment) and 'wet' (experimental) projects are all possible.

Funded BBSRC DTP PhD projects are advertised between October-November here.

Funded joint Manchester-Singapore A*STAR PhD projects are advertised here.

Other vacancies will be advertised on the Universtiy Jobs website and often also on naturejobs.com

Another funding mechanism is the Newton fellowhsip scheme.

I am interested in teaching the chemistry behind biochemistry as well as aspects of biological and physical chemistry and enzymology.

Undergraduate:

I am the convenor/unit coordinator of CHEM10111 - Fundamentals of Chemistry, which aims to give biologists an introduction to the basic principles of physical, organic and inorganic chemistry.

I teach 'enzyme catalysis and engineering' to 3rd year biochemists as part of CHEM31812 - Chemistry of biological processes.

I also be teach enzymology in CHEM20722 and CHEM401x1 and photosynthesis in CHEM30712.

Outreach:

I give occasional public lectures on 'Quantum biology' and related topics at Pint of Science, SciBAR and similar events.

Most of the group is shared/co-supervised among others in the MIB and Department of Chemistry.

Sam Hay, group leader

Dr Linus Johannissen, senior technical specialist in computational chemistry

Dr Khasim Cali, postdoc working on the EMMR project

Magnus Speirs, BBSRC DTP PhD student 2019-

Calvin Mathiah, BBSRC DTP PhD student 2020-

Jose Sena, EPSRC ICASE PhD student with with BAE Systems 2020-

Yuanxin Cao, PhD student 2021-

Emma Wall, BBSRC CASE PhD student with NPL 2022-

Jake Mitha, EPSRC ICASE PhD student with BAE Systems 2022-

Chris Field, EPSRC CASE PhD student with EnginZyme 2022-

Ayub Hareed, A*STAR PhD student with Peter Bond, NUS 2022-

Abby Richardson, MPhil student 2022-

Alumni:

James Engleback, BBSRC CASE PhD student 2017-22, now at Sygnature Discovery

Dr Andreea Iorgu, 'MAGIC' PhD 2018 and then postdoc 2018-22, now a postdoc in Jason Mickefield's group

Dr Murali Shanmugam, MIB EPR facility, now based in the EPSRC National Service for Electron Paramagnetic Resonance Spectroscopy

Sylwia Czarnota, 'MAGIC' PhD 2018, now at Université de Montréal  

Aled Roberts, postdoc 2018-19, now a FBRH fellow

Andrew Stewart, 'MAGIC' PhD 2018, now at Emory University

Stefan Görlich , postdoc 2015-17, now at TU Dresden.

Claudio dos Santos, PhD 2016, now at Waters Corp.

James Longbotham, postdoc 2014-15, now at UCSF.

Julius Rentergent, PhD 2015, now at Brandeis University.

Max Driscoll, postdoc 2011-2014