Protein Unfolding Transitions in an Intrinsically Unstable Annexin Domain: Molecular Dynamics Simulation and Comparison with Nuclear Magnetic Resonance Data

Abstract

Unfolding transitions of an intrinsically unstable annexin domain and the unfolded state structure have been examined using multiple approximately 10-ns molecular dynamics simulations. Three main basins are observed in the configurational space: native-like state, compact partially unfolded or intermediate compact state, and the unfolded state. In the native-like state fluctuations are observed that are nonproductive for unfolding. During these fluctuations, after an initial loss of approximately 20% of the core residue native contacts, the core of the protein transiently completely refolds to the native state. The transition from the native-like basin to the partially unfolded compact state involves approximately 75% loss of native contacts but little change in the radius of gyration or core hydration properties. The intermediate state adopts for part of the time in one of the trajectories a novel highly compact salt-bridge stabilized structure that can be identified as a conformational trap. The intermediate-to-unfolded state transition is characterized by a large increase in the radius of gyration. After an initial relaxation the unfolded state recovers a native-like topology of the domain. The simulated unfolded state ensemble reproduces in detail experimental nuclear magnetic resonance data and leads to a convincing complete picture of the unfolded domain.

Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound

“…In addition, the radius of gyration (Rg) was calculated for the SARS-CoV-1 S protein-ACE2 complex for both its unbound and bound state with emodin. Rg reflects protein compactness and a large body of evidence is available describing that an increase of Rg compared to a stable folded state is typically associated with unfolding processes and complex dissociation [41][42][43]. The complex in the bound state with emodin showed higher Rg values compared to the unbound complex, particularly at the level of the S protein (Figure 5C,D).…”

A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the β-sheet of murine PrP: An X-ray and molecular dynamics simulation study

“…(b) Explicit solvation used the canonical ensemble (NVT) and a previously published simulation protocol (Huynh et al, 2002). The treatment of long-range interactions uses atom-based force switching over a range 8-12 Å for electrostatics and a shift method for the Van der Waals forces (cutoff 12 Å ).…”

New force field for calcium binding sites in annexin–membrane complexes

“…Water molecules that were found closer than 2.7 Å to any protein (or PS molecule) atom were removed from the system giving rise to the two final systems: the ANX V/1-PS complex containing 10,261 atoms and ANX V/1 in solution containing 10,330 atoms. The long-range interactions were treated as suggested by some previous works 30 (and references therein). The Coulomb interactions were truncated with atom-based force switching over a range of 8 to 12 Å, and Van der Waals interactions were treated by the shift method with a cutoff 12 Å.…”