QM/MM modeling of ligninolytic enzymes
Lead Research Organisation:
University of St Andrews
Department Name: Chemistry
Abstract
State-of-the-art quantum-mechanical/molecular-mechanical methods will be applied to model, rationalise and predict redox potentials of enzymes involved in oxidative degradation of lignin. Special attention will be given to heme-based oxidases such as lignin peroxidase, manganese peroxidase and versatile peroxidase, and to the way how their protein environment tunes the oxidative power of the oxoiron(IV) active centre. The precise location of charged residues (also as function of pH) is expected to be crucial and it should be possible to identify hotspots for possible mutations that could enhance the redox potential and, hence, the ligninolytic activity of these enzymes. Selected mutant proteins will be studied computationally through homology modeling to identify the most promising targets for possible subsequent bioengineering.
Attendance of STFC-sponsored "DL_Software Training Workshop " in Daresbury (5-7 Dec 2016)
Attendance of selected courses from local Postgraduate Training Course catalogue, as per requirement of PhD programme.
Attendance of STFC-sponsored "DL_Software Training Workshop " in Daresbury (5-7 Dec 2016)
Attendance of selected courses from local Postgraduate Training Course catalogue, as per requirement of PhD programme.
Organisations
People |
ORCID iD |
| Michael Buehl (Primary Supervisor) | |
| Jonathan Colburn (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/N509759/1 | 01/10/2016 | 30/09/2021 | |||
| 1790854 | Studentship | EP/N509759/1 | 01/11/2016 | 31/10/2020 | Jonathan Colburn |
| Description | - Ligninolytic peroxidases likely do not use charged amino-acids to maximise their redox potentials through electrostatic "environment" effects, at least not when these effects are considered distinct from general solvation. (i.e. precise location of charged residues is NOT important). - Electrostatic contribution to the energy from electronic embedding is a matter of definition sensitive to the choice of QM model. - Decomposition of the electrostatic contribution to the energy from electronic embedding is non-additive and should not be used in interpretation (the subject of a previous paper). - Attempts to engineer better (more oxidising) ligninolytic peroxidases should not focus on altering charged amino-acids for optimisation of long-range electrostatics, but instead should focus on chemical modification of heme itself or the amino-acid "shell" in its immediate vicinity. |
| Exploitation Route | - They can be used to inform further QM/MM studies of this kind - They can be used to inform attempts to engineer better enzymes for biotechnological applications |
| Sectors | Chemicals,Energy,Environment,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |