title: Temperature-induced unfolding behavior of proteins studied by tensorial elastic network model.
abstract: Motivated by single molecule experiments and recent molecular dynamics (MD) studies, we propose a simple and computationally efficient method based on a tensorial elastic network model to investigate the unfolding pathways of proteins under temperature variation. The tensorial elastic network model, which relies on the native state topology of a protein, combines the anisotropic network model, the bond bending elasticity, and the backbone twist elasticity to successfully predicts both the isotropic and anisotropic fluctuations in a manner similar to the Gaussian network model and anisotropic network model. The unfolding process is modeled by breaking the native contacts between residues one by one, and by assuming a threshold value for strain fluctuation. Using this method, we simulated the unfolding processes of four well-characterized proteins: chymotrypsin inhibitor, barnase, ubiquitein, and adenalyate kinase. We found that this step-wise process leads to two or more cooperative, first-order-like transitions between partial denaturation states. The sequence of unfolding events obtained using this method is consistent with experimental and MD studies. The results also imply that the native topology of proteins "encrypts" information regarding their unfolding process. Proteins 2016; 84:1767-1775. © 2016 Wiley Periodicals, Inc.
authors: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Amit
authors: A
authors: Srivastava
authors: Department of Biotechnology Engineering, Ben-Gurion University of The Negev, Beer Sheva, 84105.|The Ilse Katz Institute for Meso and Nanoscale Science and Technology, Ben-Gurion University of The Negev, Beer Sheva, 84105, Israel.
authors: Rony
authors: R
authors: Granek
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry*; D000465:Algorithms; D020816:Amino Acid Motifs; D016880:Anisotropy; D000069977:Bacillus amyloliquefaciens / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins; D004548:Elasticity; D006801:Humans; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry*; D011489:Protein Denaturation; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D012260:Ribonucleases / Q000737:chemistry*; D011198:Solanum tuberosum / Q000737:chemistry / Q000378:metabolism; D013696:Temperature; D013816:Thermodynamics; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D010940:Plant Proteins; D025801:Ubiquitin; C023578:proteinase inhibitor I (plants); D000263:Adenylate Kinase; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease
keywords: biopolymers; bond bending; crack propagation; elastic network models; protein unfolding; twist elasticity