On 12 January 2011 06:04, bharat lal monu46010@yahoo.com wrote:
> Hi, > > I have a question regarding modeling the loop of an already determined > structure of a protein *de novo. *I want to change the entire sequence of > the loop regions of the protein with random sequences and also I want to > extend the length of the loops in the protein structure. I have searched > through a lot of papers but I am not able to find any specific paper about > such an approach.. So, I want to know can Modeller help in solving this > problem and also I will be highly obliged if anybody can refer me to some > good paper on De novo loop modeling .. > > 1. Remove the loop region form your template. 2. Align the resulting template sequence with the same sequence but include the desired aa sequence. The alignment shoud look like this:
>template AGF--------GHK >target AGFRRKTYDERLGHK
where RRKTYDERL is the sequence of the loop you want to model.
3. The use loopmodel build a new model and the loop conformation ab initio as in this example:
http://www.salilab.org/modeller/manual/node32.html
homology models will be named as "target.B9999*.pdb" whereas loop models "target.BL999*.pdb"
4. Create as much as possible loopmodels by setting the following parameters accordingly:
a.loop.starting_model a.loop.ending_model
Also bear in mind that loop modeling works well for loop <12 aa. When the length exceed ~15 aa the reliability drops abruptly. I would recommend searching the mailing list about loop modeling, this subject has been covered extensively in the past.
Thomas
PS: QUARK ab initio server has a new option that allows distance restraints. The problem is that it has a 200 aa limit and you have to include the surrounding environment of the loop in order to get an accurate prediction. I intend to try this option soon, so I'll keep you posted.