Critical phenomena in the temperature-pressure-crowding phase diagram of a protein

• Published in: arXiv.org 2019-06
• Main Authors: Gasic, Andrei G, Boob, Mayank M, Prigozhin, Maxim B, Homouz, Dirar, Daugherty, Caleb M, Gruebele, Martin, Cheung, Margaret S
• Format: Article
• Language: English
• Subjects: Computer simulation; Critical phenomena; Critical point; Critical temperature; Crowding; Free energy; Kinases; Mapping; Phase diagrams; Phases; Proteins; Structural integrity; Variation
• ISSN: 2331-8422
• DOI: 10.48550/arxiv.1906.03660

In the cell, proteins fold and perform complex functions through global structural rearrangements. Function requires a protein to be at the brink of stability to be susceptible to small environmental fluctuations, yet stable enough to maintain structural integrity. These apparently conflicting behaviors are exhibited by systems near a critical point, where distinct phases merge \(-\) a concept beyond previous studies indicating proteins have a well-defined folded/unfolded phase boundary in the pressure-temperature plane. Here, by modeling the protein phosphoglycerate kinase (PGK) on the temperature (T), pressure (P), and crowding volume-fraction (\(\phi\)) phase diagram, we demonstrate a critical transition where phases merge, and PGK exhibits large structural fluctuations. Above the critical temperature (Tc), the difference between the intermediate and unfolded phases disappears. When \(\phi\) increases, the Tc moves to a lower T. We verify the calculations with experiments mapping the T-P-\(\phi\) space, which likewise reveal a critical point at 305 K and 170 MPa that moves to a lower T as \(\phi\) increases. Crowding places PGK near a critical line in its natural parameter space, where large conformational changes can occur without costly free energy barriers. Specific structures are proposed for each phase based on simulation.