Comparative modeling of protein structure based on a homolog of known structure offers the most viable alternative to experimental structure determination. However, achieving the quality of the homology model comparable to experimental structures is a challenge. MIA suite provides two programs, Chiron and Loop, that harness the efficient sampling capability of the physically accurate all-atom DMD simulations to ensure your homology models are of structural quality comparable to experimental structures.


Loop. In the pipeline of homology model building, adding loops to the protein structure is an important and technically challenging step. The loop module utilizes programs that automate DMD for the specific purpose of loop-building.

Chiron. Chiron is the first program in its class that utilizes an energetic measure for steric clashes: the "clash-score". Moreover, by using a distribution of the "clash-score" of high-resolution structures, Chiron can report the Z-score of a given structure in terms of its clash-score. Once it has been identified that a given structure features unacceptable Z-score, Chiron uses DMD to minimize the clash-score. DMD is optimized such that, using specific parameters, Chiron can be used to resolve even severe clashes that cause traditional MD to fail. Additionally, Chiron causes minimal perturbation (less than 1 Å Cα RMSD in a benchmark set of structures with severe clash-scores). Thus, it is the ideal tool to ensure homology models have physiologically acceptable clash-scores.


  • Chiron can minimize structures with severe clashes, where other methods fail.
  • In benchmark tests, Chiron is able to resolve clashes from the homology models within 1Å of the initial model and yet not drift away from the native structure.
  • Chiron is the first program to use an energetic measure for steric clashes, which is a more realistic way to evaluate quality of a protein structure

Robust Clash Minimization
Figure 1
Q13823 model after Chiron Minimization
The efficacy of Chiron in minimizing clashes in protein structure is demonstrated for the homology model of Q13823, whose initial model has a clash-ratio of 0.13, much higher than that seen in experimental structures (<0.02). The minimized structure has a clash-ratio of 0.018, within one standard deviation of the mean clash-score of high-resolution structures.
Chiron works where traditional MD fails
Figure 2
Structural refinement of 1GFF
PDB ID 1GFF is not amenable for MD simulations due to infinite force at Proline 138. We observe severe clashes between CG1 of V20 from a bound peptide and CD, CG atoms of Proline 138 (A). One of these clashes is represented as spheres (B); the structure from PDB is colored green, while the structure obtained after DMD minimization is colored blue. DMD minimization completely removes these clashes (C).


Chiron: S. Ramachandran, P. Kota, F. Ding, and N. V. Dokholyan, "Automated minimization of steric clashes in protein structures." PROTEINS: Structure, Function and Bioinformatics, 79: 261-270 (2011)

Gaia: P. Kota, F. Ding, S. Ramachandran, and N. V. Dokholyan, "Gaia: Automated quality assessment of protein structure models." Bioinformatics, 27: 2209-2215 (2011)


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