Photochemistry in the Membrane: Quantum Chemical Studies of Fluorophores In Situ

Lead Research Organisation: University of Nottingham
Department Name: Sch of Chemistry


Some of the most thrilling images of cells come from fluorescence studies, in which green fluorescent protein (GFP) has been attached to biomolecule of interest. The impact of such studies is undeniable, but smaller fluorophores would be less invasive and potentially more faithful reporters of the molecular environment. The development of new fluorophores should ideally be built on a first principles' understanding of the photochemistry of molecules in membrane environments. This proposal takes recent advances in quantum chemistry / selected subspace time-dependent density functional theory (pioneered by, Dr Besley, one of the co-applicants) / and will apply it to a series of molecules and molecular environments, culminating in the study, in an atomistic model of a membrane, of 5-hydroxytrytophan and truncated di-9-ANEPPS: two optical probes of particular emerging interest.This project poses several computational challenges. Electronic excited state calculations, even on isolated molecules, are often not trivial. The incorporation of the molecular environment explicitly into the excited state calculations is a relatively new undertaking, and we propose to extend the approach beyond current limitations (in terms of numbers of atoms and electrons) by exploiting new developments in TDDFT.The application of quantum chemical methods to study biological processes is without doubt an area of research that will grow rapidly in the near future. In conjunction with novel experiments, this will provide detailed and quantitative insight into many biological and medical processes. We propose to use state-of-the-art quantum chemical methods to study the interaction between molecule and membranes through calculations of both the ground and excited states of the fluorophore. These calculations should enable a detailed picture of the molecular-membrane interaction to be established and provide qualitative insight into these exciting new experiments and ultimately our understanding of biological processes at the membrane interface.


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Robinson D (2011) Di-8-ANEPPS emission spectra in phospholipid/cholesterol membranes: a theoretical study. in The journal of physical chemistry. B

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Robinson D (2009) Electronic structure of 5-hydroxyindole: from gas phase to explicit solvation. in The journal of physical chemistry. B

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Robinson D (2011) Water order profiles on phospholipid/cholesterol membrane bilayer surfaces in Journal of Computational Chemistry

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Robinson D (2009) Calculating the fluorescence of 5-hydroxytryptophan in proteins. in The journal of physical chemistry. B

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Robinson D (2010) Modelling the spectroscopy and dynamics of plastocyanin. in Physical chemistry chemical physics : PCCP

Description Through quantitative first-principles calculations, we generated new insight into the electronic spectroscopy of fluorophore probes in cell membranes and chromophores in proteins.
Exploitation Route They will inform future research in the area.
Sectors Chemicals,Pharmaceuticals and Medical Biotechnology

Description This project tackled a problem of both applied and fundamental importance. We elucidated a number of principles governing the relationship between the electronic excited states of several fluorophores of interest and their surrounding molecular environment. This should be of particular interest and utility to experimental biophysicists and also experimental cell biologists (ie. as molecular probes may be designed that are more revealing of the cellular environment) undertaking such characterisations. It will also be beneficial to the molecular simulation community to have another direct link between their models and experimental measurements.
First Year Of Impact 2011
Sector Chemicals,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

Description University of Nottingham
Amount £61,813 (GBP)
Funding ID 2/SRF/2010/0603 
Organisation University of Nottingham 
Sector Academic/University
Country United Kingdom
Start 05/2011 
End 05/2014