OMSys: Towards a systems model of a bacterial outer membrane

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry


Many bacteria have an outer membrane which is the interface between the cell and its environment. The components of this membrane are well studied at an individual level, but there is a need to model and understand the outer membrane as a whole. In this project we aim to develop such a model of a bacterial outer membrane, linking computer simulations of the component molecules through to a more 'systems biology' approach to modelling the outer membrane as a whole. Such an approach to modelling an OM must be multi-scale i.e. it must embrace a number of levels ranging from atomistic level modelling of e.g. the component proteins through to higher level 'agent-based' modelling of the interplay of multiple components within the outer membrane as a whole. The different levels of description will be integrated to enable predictive modelling in order to explore the roles of outer membrane changes in e.g. antibiotic resistance.

Technical Summary

In this project we aim to develop a model of a bacterial outer membrane (OM), linking biomolecular simulations through to computational systems biology approaches. Such an approach to modelling an OM must be multi-scale i.e. it must embrace a number of levels: (i) atomistic level modelling of protein/ligand interactions; (ii) coarse-grained modelling of both outer membrane proteins and lipoproteins and of their lipopolysaccharide/phospholipid/peptidoglycan environment; and (iii) higher level e.g. agent-based modelling of the interplay of multiple components within the OM as a whole. The different levels of description will be integrated to enable predictive modelling of bacterial OMs in order to explore the roles of OM changes in e.g. antibiotic resistance and envelope stress responses.


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Description We have discovered that the different components of the bacterial outer membrane, move at different rates. They also have different permeability characteristics which means that incoming or outgoing drug molecules will experience very different environments in the two leaflets of the membrane.
Exploitation Route Our findings will be invaluable for future design of antibiotics
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

Description Travel grant presented to the post doctoral researcher funded on this grant so he could attend the US Biophysical Society annual meeting in San Diego in February 2012.
Amount £400 (GBP)
Organisation Biochemical Society 
Sector Charity/Non Profit
Country United Kingdom
Title Lipid parameters 
Description We have contributed our force field files for all computational models of lipopolysaccharide and other membrane components developed as part of this project, to the freely available, online database; 'lipid book'. 
Type Of Material Model of mechanisms or symptoms - in vitro 
Year Produced 2012 
Provided To Others? Yes  
Impact The parameters are actively being used by other groups, the paper which contains the citation for the models has been cited over 50 times. The database is described here 
Description CCPB US-partnership award 
Organisation U.S. Department of Energy
Department Pacific Northwest National Laboratory
Country United States 
Sector Public 
PI Contribution The PDRA funded by this grant was awarded a grant by CCPB (now defunct) to visit a laboratory at the Pacific Northwest National Laboratory to gain experience of creating atomistic models of lipopolysaccharide; and essential component of the OMSys project.
Start Year 2010
Description OMsys collab with Peter Bond 
Organisation Agency for Science, Technology and Research (A*STAR)
Department Bioinformatics institute (BII)
Country Singapore 
Sector Academic/University 
PI Contribution This collaboration involves running and analysing simulations of (a) atomistic simulations of antimicrobial peptides and (b) large coarse-grain vesicles containing a mixture of phospholipids, both with the aim of exploring lipid-protein interactions in bacterial membranes. We set up and performed the simulations for both parts of the project, we also performed most of the analysis. The original idea came from us, as it was part of the OMSys project.
Collaborator Contribution (1) Analysis of antimicrobial peptides based on the PIs experience (2)New computational tools to analyse large curved membranes. They helped us write the manuscript which is currently in review at PLoS ONE.
Impact Papers: 1- PLoS Comput Biol. 2015 Apr 17;11(4):e1004180. doi: 10.1371/journal.pcbi.1004180. eCollection 2015. Interaction of the antimicrobial peptide polymyxin B1 with both membranes of E. coli: a molecular dynamics study. Berglund NA1, Piggot TJ2, Jefferies D2, Sessions RB3, Bond PJ4, Khalid S2. 2-PLos ONE: How many is a crowd? The dynamics of crowded vesicles are altered by their membrane composition Holbrook, Huber, Piggot, Bond, Khalid This is currently in review.
Start Year 2011
Title PyCGTool 
Description PyCGTool enables parameterisation of coarse-grain molecules, systematically from atomistic trajectories. The paper describing the first version of the software is available here: The software has since been updated and is now further being improved to add procedures for automated mapping of the coarse-grain models from their atomistic equivalents. 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact The software has been used by several groups to parameterise new molecules (e.g. cyclodextrins). We have used it to parameterise lipopolysaccharide molecules. 
Description Advanced technology to support research, innovation and economic growth in the UK 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Reform hosted a policy roundtable on the opportunities for advanced technology in the UK in May 2019, with the kind support of Hewlett Packard Enterprise. The session was introduced by Chris Skidmore MP, then Minister of State for Universities, Science, Research and Innovation, and Professor Mark Parsons, Director at the Edinburgh Parallel Computing Centre.

The Minister stressed the importance of international collaboration in R&D, reaffirming the UK's ambition to strengthen and enrich existing
partnerships, as well as to develop new global partnerships - as outlined in the then recently announced International Research & Innovation
Strategy. The discussion also focused on the opportunities the upcoming Comprehensive Spending Review would offer to the science, research and innovation sectors, and on the need to build a strong case for. investment in emerging technologies - including quantum technology, performance computing (HPC) and robotics.

During this meeting it was highlighted that High-performance computing is considered a game-changing technology, which will be fundamental
to the UK's ability to maintain its global competitiveness in the science, research and innovation sectors.
Year(s) Of Engagement Activity 2019
Description Hamied Foundation UK-India Antimicrobial Resistance Meeting 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I was part of an expert panel of scientists and medics from the UK and India assembled to discuss how we can (a) combat existing antimicrobial resistance and (b) prevent or slow down the development of resistance in future. The chief medical officer of the UK was also in attendance and a gave talk. Collaborations between scientists from both countries were established and existing ones were strengthened. An emerging theme was that all levels must be addressed, from atoms and molecules through to patients, communities and the environment. I helped establish this theme.
Year(s) Of Engagement Activity 2019
Description Pint of Science talk: Making movies of Bacterial membranes 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I gave a talk in a pub to an audience consisting of members of the general public who had bought tickets to the event. The talk explained some of the science behind antimicrobial resistance followed by some details of my own work in terms of 'making movies' of the bacterial membranes so we can understand how they protect bacteria. I talked about how we have to understand the membranes in molecular detail if we are to design new drugs with the ability to permeate across these membranes. Audience members said they had a much better understanding of how they must not abuse antibiotics, after the talk.
Year(s) Of Engagement Activity 2017