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What is a superbug?

You may have heard of hospital superbugs. They are bacteria like MRSA or c.diff that cannot be treated using ordinary medicines. People can catch these infections when they are being treated in hospital and it makes the patient very ill and sometimes leads to death.

Bacteria, like all living organisms, evolve to survive in their environment. Unfortunately, superbugs have evolved so that antibiotics no longer kill them.

MRSA bacteria

How can a computer kill a superbug?

By helping scientists develop new drugs that will kill resistant bacteria.

I am working on an antibiotic called nisin. When the nisin is first made it is like a long strand but to be able to kill bacteria it must fold up into a shape with two circles. Imagine taking a straight piece of wire and bending it into a frame for a pair of spectacles, this is similar to the microscopic folding process. Small changes to the position of some of the atoms in the nisin molecule change how it folds. Making all the possible nisin molecules in the laboratory would be very expensive and time consuming. By running simulations I can see which molecules will make the shape I want and then I can tell my colleagues who are making and testing new antibiotics which ones to focus their work on – saving them time, effort and money

I run lots of different type of simulations:

Molecular dynamics simulations that look at how atoms can move.
Docking simulations that predict how molecules interact with each other.
Some simulations use Newton’s Laws of Motion…
…but others use Quantum Mechanics, a branch of physics where electrons behave in weird and unexpected ways.

This YouTube channel has animations of simulations made by scientists working in my research area:

Do you work with any other molecules?

I am also trying to understand a molecule called the ileal lipid binding protein (ILBP for short) which is in the gut and absorbs bile salts. Bile salts are made in the body from cholesterol and help us to digest fatty foods. When bile salts are absorbed by ILBP they are recycled, meaning that the body will not convert as much cholesterol into new bile salts. If we can find a way of stopping ILBP absorbing bile salts then we would decrease the amount of cholesterol in the body. This would be really good news as 6 out of 10 adults in the UK have high cholesterol and it is strongly linked to heart disease.

This is a picture of ILBP. The purple coils on top act as a gate that allows bile salts to enter and leave the inside of the protein. I have been running computer simulations of ILBP under different conditions, such as changing the type of bile salt or pH level, to understand what makes the gate open and shut. Once this is understood other scientists who work on developing medicines can use the information to find a drug that will stop ILBP absorbing so many bile salts.

What is your subject called?

Computational biophysical chemistry. This basically means I use IT, physics, biology and chemistry to understand how these molecules work. Physics so that I know how the molecules move, biology to know how they work in the body, chemistry to know how the atoms are bonded to each other and IT so I can simulate it all.

When you study science at school there is a clear distinction between physics, chemistry, biology, maths and IT. But to full-time scientists there are lots of areas where the subjects overlap.