diff --git a/education/molmod_online/modelling.md b/education/molmod_online/modelling.md index 7a3f37bf..cc54569e 100644 --- a/education/molmod_online/modelling.md +++ b/education/molmod_online/modelling.md @@ -121,16 +121,20 @@ The following tab, **Family & Domains**, lists structural and domain information For the mouse MDM2 protein, it shows that it contains a *SWIB* domain and two *zinc fingers* and that it interacts with proteins such as USP2, PYHIN1, RFFL, RNF34, among others. Additional information displayed in the text offers additional insights on binding partners and interfaces. - - Which region(s) of MDM2 bind p53 and which of those bind to the trans-activation domain? - From the introduction, you know that our region of interest in MDM2 interacts with the trans-activation region of p53 and does _not_ ubiquitinate it. The small print under the "Domain" header gives clues regarding possible p53 interfaces: -"Region I is sufficient for binding p53"; +"Region I (1-110) is sufficient for binding p53"; "the RING finger domain [...] is also essential for [MDM2] ubiquitin ligase E3 activity toward p53". -It seems, therefore, that _Region I_ is our modelling target, but besides this annotation, it +After, in the **Family and domain databases** sub-section, +have a look at [Pfam PF02201](https://www.ebi.ac.uk/interpro/entry/pfam/PF02201/) or [InterPro IPR003121](https://www.ebi.ac.uk/interpro/entry/InterPro/IPR003121/) entries to get more information about the composition of the first Region (1-110). + + + Which region(s)/domains(s) of MDM2 bind p53 and which of those bind to the trans-activation domain? + + +It seems, therefore, that the _SWIB_ domain is our modelling target, but besides this annotation, it is not listed anywhere on the UniProt page. While this mystery has plenty of possible solutions, the easiest of which would be to search for a publication on the MDM2 domain organisation. Keep to the UniProt page to find an answer. @@ -405,15 +409,15 @@ The interface conservation can be quite useful in defining how well template int Thus, the closes homologues should reach the lowest interface conservation values in the highest possible identity cut-off. + +Which template(s) show the evolutionary most conserved interface? Is this good? + + In the **Sequence Similarity** plot, templates are clustered by their sequence identity and are represented by circles. Thus, templates with high sequence identity form clusters further away from clusters of lower sequence identity. The distance between templates is proportional to the sequence identity between them. You can see the name and the structure of each template by hovering over with your mouse. - -Which templates show the evolutionary most conserved interface? Is this good? - - If one selects multiple templates by checking the window in the **Templates** tab, their sequence alignment is shown in **Alignment of Selected Templates**. By clicking on the `More` button, one can see the complete list of templates not shown in this preview, download the Template Search Log or PDB structures of selected templates. diff --git a/education/molmod_online/simulation.md b/education/molmod_online/simulation.md index f14694d8..6b1e0017 100644 --- a/education/molmod_online/simulation.md +++ b/education/molmod_online/simulation.md @@ -78,7 +78,7 @@ expanded to a three-dimensional space. $$ \begin{equation} - \frac{\delta^2 x_{i}}{\delta t^2} = \frac{F_{x_{i}}}{m_i} + \frac{d^2 x_{i}}{d t^2} = \frac{F_{x_{i}}}{m_i} \end{equation} $$ @@ -117,9 +117,9 @@ algorithm first calculates the forces acting on each atom. From that force, one acceleration of the atoms and combine these with their positions and velocities at time $$ t $$ to yield a new set of positions and velocities. The _time_ between the old and new positions is fixed and parametrized at the beginning of the simulation. In biomolecular simulations, the time step -($$ \delta t $$) is usually set to 2 femtoseconds (*fs*), which is large enough to sample significant dynamics +($$ \Delta t $$) is usually set to 2 femtoseconds (*fs*), which is large enough to sample significant dynamics but not as large as to cause problems during the calculations. Too big of a time step can lead to severe issues, such as two atoms -overlooking each other, or even end up overlapping! At $$ t + \delta t $$, a new set of forces is +overlooking each other, or even end up overlapping! At $$ t + \Delta t $$, a new set of forces is calculated and so on. The simulation finishes only when there have been enough steps to reach the desired simulation time. Besides all these calculations, biomolecular simulations try to also simulate the conditions inside cells, namely regarding temperature and pressure. There are special @@ -922,7 +922,7 @@ with your name or initials. - Run the production MD! This will take a few hours to complete. + Run the production MD! This will take some time, from a few hours to a few days - depending on the amount of computing resources available.