Molecular Dynamics Simulations of Protein Unfolding

Professor Makarov and his collaborators and students are interested in the way in which load-bearing proteins (e.g., titin and others found in muscle tissue) and proteins with similar structure resist mechanical forces that tend to unfold them. Such forces are found, for example, in the pore structure of the proteasome, the subcellular complex that unfolds and degrades proteins no longer needed in cellular metabolism. Makarov's collaborators at several universities are performing unfolding experiments using atomic-force microscopy, while the calculations run by Makarov and his students on TACC resources simulate such experiments and also the natural (proteasomic) unfolding process.

The work is computationally intensive because the time scales over which biological unfolding occurs are much longer than can be simulated with exact atomistic models. Makarov and his students use minimalist models in which amino acid residues are each represented as single atoms. Their simulations nevertheless bear excellent resemblance to the laboratory experiments. For more information on Makarov's research, see Microscopic but Mighty: Mechanical Marvels.