2026-09-20T11:19:46Zhttps://iris.unica.it/oai/requestoai:iris.unica.it:11584/2487382022-10-20T09:55:20Zcom_11584_207615com_11584_111066col_11584_207612
Computational methods for transport properties
SALIS, SAMUELE
RUGGERONE, PAOLO
Settore FIS/05 - Astronomia e Astrofisica
Through antimicrobial resistance many bacteria can survive to an
ever larger number of antibiotics. This is true in particular for a category
of bacteria classified as gram–negative. These kinds of bacteria
differ from the other ones by the presence of an outer membrane,
which is able to protect them from the fast access (and consequently
the action) of any antibiotics. The increasing capability of antibiotics
to survive to many kinds of drugs has given rise to the Multiple
Drug Resistance (MDR). New antibiotics could help to mitigate
the MDR problem, but the poor understanding of permeability
through outer membranes has given an ever littler number of new
patented antibiotics. This is due to a lack of experimental methods
which are able to explain with a sufficient detail the permeation
and, on the other side, to the difficulty in reaching the typical time
scales (ms or even more) of these processes. The category of antibiotics
studied in this thesis can permeate the membrane crossing
some porins (beta barrel proteins nestled in bacterial outer membrane)
so the permeation happens when we observe a transport of
the antibiotic through a porin.
In this thesis we will focus on some computational methods,
which are suitable to increase our understanding of transport processes.
We will start with a post elaboration algorithm, that can
be used to extract from an electrophysiology time series transport
events apparently lower than the experimental device temporal sensitivity,
continuing with another post elaboration algorithm that allows
to extract the real transition time from a metadynamics simulation, skipping in this way the timescale problem in computer
simulations, and we will finish with an ultra coarse grained model,
that can be used to study the transport properties through a bacterial
channel. Finally we will list the results obtained using the three
aforementioned methods and we will summarise this thesis with
the conclusions.
Through antimicrobial resistance many bacteria can survive to an
ever larger number of antibiotics. This is true in particular for a category
of bacteria classified as gram–negative. These kinds of bacteria
differ from the other ones by the presence of an outer membrane,
which is able to protect them from the fast access (and consequently
the action) of any antibiotics. The increasing capability of antibiotics
to survive to many kinds of drugs has given rise to the Multiple
Drug Resistance (MDR). New antibiotics could help to mitigate
the MDR problem, but the poor understanding of permeability
through outer membranes has given an ever littler number of new
patented antibiotics. This is due to a lack of experimental methods
which are able to explain with a sufficient detail the permeation
and, on the other side, to the difficulty in reaching the typical time
scales (ms or even more) of these processes. The category of antibiotics
studied in this thesis can permeate the membrane crossing
some porins (beta barrel proteins nestled in bacterial outer membrane)
so the permeation happens when we observe a transport of
the antibiotic through a porin.
In this thesis we will focus on some computational methods,
which are suitable to increase our understanding of transport processes.
We will start with a post elaboration algorithm, that can
be used to extract from an electrophysiology time series transport
events apparently lower than the experimental device temporal sensitivity,
continuing with another post elaboration algorithm that allows
to extract the real transition time from a metadynamics simulation, skipping in this way the timescale problem in computer
simulations, and we will finish with an ultra coarse grained model,
that can be used to study the transport properties through a bacterial
channel. Finally we will list the results obtained using the three
aforementioned methods and we will summarise this thesis with
the conclusions.
2017-03-01
info:eu-repo/semantics/doctoralThesis
http://hdl.handle.net/11584/248738
eng
info:eu-repo/semantics/openAccess
Università degli Studi di Cagliari