Dear Tonapha,

As recommanded, Modeller or SwissModel would the best to prepare 3D models of your candidates (if you don't have the 3D structure), and make mutants.

http://salilab.org/modeller/

http://swissmodel.expasy.org/

Modeller needs a license, but is free for university.

Then, you can compare the wild-type and the mutants using different tools. For example, you can estimate the change in electrostatic patches (with APBS in PyMOL). Or estimate the stability effect of the mutation (FoldX, Cupsat).

http://cupsat.tu-bs.de/

http://foldx.crg.es/

We recently published a review in this topic, where we list some of these resources:

Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes

Romain A. Studer, Benoit H. Dessailly and Christine A. Orengo

http://www.biochemj.org/bj/449/bj4490581.htm

The review is free for download until the 1st of February.

Hope that helps you!

Romain

There are some good softwares which can predict the effect of amino acid changes on protein structure and function . I will suggest you to go through the following links:

1) http://www.ics.uci.edu/~baldig/mutation.html

2) http://sift.jcvi.org/

You can also crosscheck the results by another way also:

1) Predict structures for both the sequences (wild type and mutated) by either threading or homology modeling.

2) Check with structural alignment to see deviation in structures.

Dear Tonapha,

First, for modelling 3D structure u can go for swiss modeller for preliminary analysis which is freely available, other may be I-Tasser etc. U can validated your output model on NIH SAVES structural validation server. For checking evolution at molecular level, u can first check by sequence alignment comparison (Clustal W may work fine and freely available) and then substitute particular amino acid in sequence and again model and validate them and visualize changed structure on pymol viewer. Next easy way is you can use Consurf server (http://consurf.tau.ac.il/) and put your amino acid sequence alignment file generated on clustal W. If your protein sequence family or homologous protein have crystal structure on PDB database u can input PDB id of that protein as well. The programe will give output of sequence alignment as well as modelled structure in color code form of evolutionary conserved to diverse amino acid substitution.

Hope this will answer your query.

gud luck

Modeller from salilab is BEST .... will be useful for beginners and also for advanced users.

Cheers

Chimera: very easy to use, incorporates Modeller which is not at all easy to use, and produces publication-quality images in a few clicks.

http://www.cgl.ucsf.edu/chimera/

Chimera is easy to use and based in modeller.

There are servers too, like the I-Tasser by the Yang Zhang Lab. Tasser has won the latest CASPs, and it's (from my point of view) the best one to predict a structure. Check it out, it allows you to submit your sequence and chose a template in case you have an homologous structure, or the server will choose the most suitable template from the PDB. Once you get your results you'll be able to download data as a pdb file to visualize and edit in the software you want (I love Pymol but VMD and others are good as well).

Modeller is awesome but it wont do if you dont have a license. If you wish to model small number amino acid changes only, with an already given template structure of the same protein you can use Scwrl4. THe progam will assume that your backbone remains fixed (from the template) and will model the side chains of the amino acids and generate a new pdb file. Use modeller if you have no structure of your protein for starters.

Dear Tonapha,

As recommanded, Modeller or SwissModel would the best to prepare 3D models of your candidates (if you don't have the 3D structure), and make mutants.

http://salilab.org/modeller/

http://swissmodel.expasy.org/

Modeller needs a license, but is free for university.

Then, you can compare the wild-type and the mutants using different tools. For example, you can estimate the change in electrostatic patches (with APBS in PyMOL). Or estimate the stability effect of the mutation (FoldX, Cupsat).

http://cupsat.tu-bs.de/

http://foldx.crg.es/

We recently published a review in this topic, where we list some of these resources:

Residue mutations and their impact on protein structure and function: detecting beneficial and pathogenic changes

Romain A. Studer, Benoit H. Dessailly and Christine A. Orengo

http://www.biochemj.org/bj/449/bj4490581.htm

The review is free for download until the 1st of February.

Hope that helps you!

Romain

I've seen NAMD it's a good option. Here: http://www.ks.uiuc.edu/Research/namd/

NAMD is a tool for molecular dynamics, like Amber, Charmm and Gromacs. This is the best option to view the effect of a mutation, but it requires much more competences and computational time than other options previously cited.

Hi

As per I know if its a protein alone, then CHARMM (NAMD) or GROMACS will work better. These two MD tools are for minimization of the protein once you have the mutant structures.

If you dont have structure and since only few mutations are there, you can use MODELLER, which is freely available (you need to apply for the license key). Otherwise PHYRE or SPDBV or ITASSER (takes alot of time, but the best at present (my opinion)) can be used to find the mutant structure.

Dear All,

Thank you very much for all your suggestion. I will try those programs to see which works for me and easy to work on.

Please, try the program we used in:

Hemleben, V., Dressel, A., Epping, B., Martens, S., Lukacin, R ., Austin, M.B.: Characterization and structural features of a chalcone synthase mutation in the white-flowering mutant line 18 of Matthiola incana R.Br. (Brassicaceae). Plant Mol. Biol. 55: 455-465 (2004)

I used the geno3D. Its is very nice and in a few days you will have your 3d structures. you can find it in the page of Expasy (SiB Bioinformatics Resource):

http://www.expasy.org/tools/

I hope this helps you!!!

Patricia

Modeller is good, but a pain to work with (you need to edit their python scripts) and Chimera is ok as an interface but doesn't allow you to access all of modeller's functions. I recommend the protinfo server http://protinfo.compbio.washington.edu/abcm/ or if you need to model a multimer: http://protinfo.compbio.washington.edu/ppc/