Hi. I am working on a unusual protein-protein docking method.
The protein structures are modeled using Homology modelling and docked using various servers. There is no complex crystal structure available which is normally required to validate the docked complex. How can I evaluate the docked results?
The complex structures are subjected to Rosetta server to calculate the iRMS, I_sc and Fnat scores. Apart from these values, is there any other quantitative measures that I can look at to validate and predict a better structure?
Or, any other methods or ways to choose better models?
Try Experimental approaches like biochemical assays or else Molecular dynamics simulations to study the stability and interactions between the enzyme-inhibitor complexes.
The simple modeling, with any methodology, never gives reliable results. The models must always be validated through molecular dynamics that gives us information on the stability of the system (and therefore its reliability). In many proteins there are very mobile unstructured segments (IDRs) that are not always highlighted by homology. These segments are often important in defining functional properties and the ability to interact.
The structure of the protein-protein complex can be assessed by indirect experiments. For instance, (i) use the current model to determine which residues are the most critical for the stability of the complex, (ii) computationally assess which mutations of these critical residues would disrupt the complex, (iii) produce the respective mutants, and (iv) use some biophysical proximity assay, such as FRET, to experimentally determine whether the complex has survived the mutations.
Hi all.. Thanks for all your valuable answers.
Here, I have performed docking of the two proteins [nearly 200 predictions] and now I need to filter them to 10 - 20 structures based on quantitative measurements [ like Irms ]. I have tried CAPRI using rosetta refining. calculated Fnat and Irms. Also calculated molprobity. Apart from these assessments are there any other important or left out assessments?
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