Simple model of pH-induced protein denaturation.
The pH-induced conformational changes of proteins are systematically studied in the framework of a hydrophobic-polar (HP) model, in which proteins are dramatically simplified as chains of hydrophobic (H) and polar (P) beads on a lattice. We express the electrostatic interaction, the principal driving force of pH-induced unfolding that is not included in the conventional HP model, as the repulsive energy term between P monomers. As a result of the exact enumeration of all of the 14- to 18-mers, it is found that lowest-energy states in many sequences change from single "native" conformations to multiple sets of "denatured" conformations with an increase in the electrostatic repulsion. The switching of the lowest-energy states occurs in quite a similar way to real proteins: it is almost always between two states, while in a small fraction of ≥16-mers it is between three states. We also calculate the structural fluctuations for all of the denatured states and find that the denatured states contain a broad range of incompletely unfolded conformations, similar to "molten globule" states referred to in acid or alkaline denatured real proteins. These results show that the proposed model provides a simple physical picture of pH-induced protein denaturation.
Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
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Hidaka
Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.
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Shimada
Institute for Biology and Mathematics of Dynamic Cellular Processes (iBMath), The University of Tokyo, Komaba, Tokyo 153-8904, Japan.|Graduate School of Mathematical Sciences, The University of Tokyo, Komaba, Tokyo 153-8902, Japan.
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Nakata
Institute for Biology and Mathematics of Dynamic Cellular Processes (iBMath), The University of Tokyo, Komaba, Tokyo 153-8904, Japan.|Graduate School of Mathematical Sciences, The University of Tokyo, Komaba, Tokyo 153-8902, Japan.
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Kodama
Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Hongo, Tokyo 113-0033, Japan.|Institute for Biology and Mathematics of Dynamic Cellular Processes (iBMath), The University of Tokyo, Komaba, Tokyo 153-8904, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
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Kurihara
Institute for Biology and Mathematics of Dynamic Cellular Processes (iBMath), The University of Tokyo, Komaba, Tokyo 153-8904, Japan.|Graduate School of Mathematical Sciences, The University of Tokyo, Komaba, Tokyo 153-8902, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Chiyoda-ku, Tokyo 102-0076, Japan.
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Tokihiro
Institute for Biology and Mathematics of Dynamic Cellular Processes (iBMath), The University of Tokyo, Komaba, Tokyo 153-8904, Japan.|Graduate School of Mathematical Sciences, The University of Tokyo, Komaba, Tokyo 153-8902, Japan.|Research Center for Advanced Science and Technology, The University of Tokyo, Komaba, Tokyo 153-8904, Japan.
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Ihara
D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011487:Protein Conformation; D059748:Proteolysis; D055672:Static Electricity