Introduction to the seminar series

G Vriend

Goals

• Illustrate a series of bioinformatics areas in which chemists, mathematicians, and physicists can constructively contribute (and find jobs…)

• Explain the very generally applicable concept: Force Field

Bioinformatics is everywhere

Metagenomics related differences

The human genome

Your future in bioinformatics

Part 2Six topics and FF

Six topics

Drug DockingHomology modellingStructure validation Energy calculations and Molecular DynamicsForce Fields starting pointSequence alignment

QC -> Force FieldQuantum chemistry is accurate, but slow.

But… everything larger than a hydrogen must be calculated using approximations.

And often these approximations take the form of a Force Field.

Part 3A FF we all know

Force Field: weather forecast

So the weather man can predict the wind-direction, but how do we teach a computer to do this?

Force Field: weather forecast

Force Field weather forecast

Force Field weather forecast

The weather forecast Force Fields thus needs:

A description of the weather now (… present situation …)

Examples of how the weather evolved in the past from many different starting situations (… to learn from …)

A computer program (… that holds the rules …)

Part 4Definition of a FF

Force Field general

More general a Force Field consists of data and a set of associated rules that can be used to describe a system and predict its future.

Force Field general

More general a Force Field consists of data and a set of associated rules that can be used to describe a system and predict its future.

So you can use a Force Field to say if a system is normal or exceptional (for a molecule that would be in or near the energy minimum versus in an excited state) and how a system will develop (for a molecule that would be calculating the energy minimum given an excited state).

Part 5A FF in chemistry - bioinformatics

Hint, we cannot use QC, so we must make approximations.

One idea would be to decompose the total force on each atom in sub-forces like electrostatic attraction/repulsion, etc.

Which sub-forces can you think of?

Force Field to calculate the energy minimum of a protein molecule?

If we assume the bond (length) and the forces over the bond to behave like a spring And please remember that the energy is the integral over the force.

Bond-length sub-force

This will come back in the Molecular Dynamics seminar.

Pictures copied from • www.almanac.com blogs.parfumswinkel.nl• www.ucsd.edu bodyfuturist.com• www.weerplaza.nl www.cancer.gov• www.cawcr.gov.au• www.crystalinks.com• www.mgms.org• Brucetarrpaintings.org• kniga-ryby-rossii.prv.pl• Nothinginbiology.org