New Publication: Energetics of Multi-Ion Conduction Pathways in Potassium Ion Channels

Can we predict the conductance of a potassium ion channel from an experimental structure?

fig-kcsa-sfIn this paper we examine the kinetic barriers experienced by potassium ions (and waters) as they move through the narrowest part of two different potassium ion channels. We examine the reproducibility of our results and test the sensitivity of the approach to changes in the method. We conclude that we are currently unable to accurately calculate the kinetic barriers to conduction for potassium channels and that other channels (such as sodium channels) may be more amenable to this approach.

This article is published in the Journal of Chemical Theory and Computation and is free to download (open access). It carries out the preparatory work necessary for a second paper on how potassium ions and water molecules move through the selectivity filter of a voltage-gated potassium ion channel.

Advertisements

GROMACS 4.6: Scaling of a very large coarse-grained system

So if I have a particular system I want to simulate, how many processing cores can I harness to run a single GROMACS version 4.6 job? If I only use a few then the simulation will take a long time to finish, if I use too many the cores will end up waiting for communications from other cores and so the simulation will be inefficient (and also take a long time to finish). In between is a regime where the code, in this case GROMACS, scales well. Ideally, of course, you’d like linear scaling i.e. if I run on 100 cores in parallel it is 100x faster than if I ran on just one.

Continue reading

GROMACS 4.6

GROMACS is a scientific code designed to simulate the dynamics of small boxes of stuff, that usually contain a protein, water, perhaps a lipid bilayer and a range of other molecules depending on the study. It assumes that all the atoms can be represented as points with a mass and an electrical charge and that all the bonds can modelled using simple harmonic springs. There are some other terms that describe the bending and twisting of molecules and all of these, when combined with two long range terms, which take into account the repulsion and attraction between electrical charges, allow you to calculate the force on any atom due to the positions of all the other atoms. Once you know the force, you can calculate where the atom will be a short time later (often 2 fs) but of course the positions have changed so you have to recalculate the forces. And so on.

Continue reading

New Publication: Detailed examination of a single conduction event in a potassium channel.

What can we learn using computational methods about how potassium ions and water molecules move through the narrowest part of a potassium channel?

fig-kvchim

In this paper, we calculate the average force experienced by three potassium ions as they move through the selectivity filter of a voltage-gated potassium channel. This allows us to identify the most probably mechanism, which includes two “knock-on” events, just like a Newton’s cradle. By examining the behaviour of the conducting waters and the protein in detail we can see how the waters rotate to coordinate one or other of the conducting potassium ions, and even get squeezed between two potassium ions during a knock-on event. We also see how the coordination number of each potassium ion changes.

This article is published in the Journal of Physical Chemistry Letters and is free to download (open access). There is an accompanying paper that is published in the Journal of Chemical Theory and Computation.