Protein unfolding modelling

Three theory papers are also included. Determinants of the Polyproline II Helix from Modeling Studies by Creamer and Campbell reexamines and extends an earlier hypothesis about Pn and its determinants. Hydration Theory for Molecular Biophysics by Paulaitis and Pratt discusses the crucial role of water in both folded and unfolded proteins. Unfolded State of Peptides by Daura et al. focuses on the unfolded state of peptides studied primarily by molecular dynamics. 

Alexa488 bound to IFABP monitored by steady-state fluorescence was fitted to a two-state reversible unfolding model. This modified protein is slightly less stable (midpoint of 4.5 M compared to 4.7 M for wild-type IFABP). 

Once the determinants of PPII helix formation are known in more detail, it will become possible to apply them, along with the known determinants of the cy-helical conformation, to the understanding of protein unfolded states. If, as suggested at the beginning of this article, protein unfolded states are dominated by residues in the PPII and cy-conformal ions, these data will allow for modeling of the unfolded state ensembles of specific proteins with a level of realism that has not been previously anticipated. 

For self-associating protein systems, third-order polynomial functions provided a good fit over the accessible range The data on AG° must show the direction of the chemical change, toward the minimum in the Gibbs function. If this proves true, the equation can be applied in the standard or nonstandard state. For protein unfolding or DNA unwinding, nonlinear models are needed Consistent with Occam s razor, the simplest description is used to describe the system, and complexity is increased only if warranted by the experimental results. 

Monte Carlo method, 210, 21 propagation, 210, 28] Gauss-Newton method, 210, 11 Marquardt method, 210, 16 Nelder-Mead simplex method, 210, 18 performance methods, 210, 9 sample analysis, 210, 29 steepest descent method, 210, 15) simultaneous [free energy of site-specific DNA-protein interactions, 210, 471 for model testing, 210, 463 for parameter estimation, 210, 463 separate analysis of individual experiments, 210, 475 for testing linear extrapolation model for protein unfolding, 210, 465. 

Two-State Model Thermodynamic Stability of Proteins (Unfolding) I 491... 

Owing to the complexity of protein structures, model compounds have often been employed in estimating thermodynamic parameters for protein unfolding. The utility of these parameters depends on the validity of the choice of a model system, i.e., how well the model system mimics the process of transferring different functional groups from the protein interior into the solvent. In principle, one would like to choose a reference state that is similar energetically to the protein interior. 

JE has shown considerable promise in steered molecular dynamics studies of the free energy landscape, and in particular it has become a popular choice for protein unfolding dynamics probably partly due to the exciting experiments carried out soon after its discovery. In this regard, the unfolding of deca-alanine has provided a relatively simple, yet realistic model that has been used to compare and test different approaches. -i"°-i5 -i i... 

Due to the changes in the dynamics, a general relationship for stochastic dynamics is not available like it is for deterministic dynamics. However, for mesoscopic systems, a mesoscopic FR is useful. Therefore, there has been much work on developing stochastic models with different conditions. Andrieux and Gaspard developed a stochastic fluctuation relation for nonequilibrium systems whose dynamics can be described by Schnakenberg s network theory (e.g. mesoscopic electron transport, biophysical models of ion transport and some chemical reactions). Due to early experimental work on protein unfolding and related molecular motors, and their ready treatment by stochastic dynamics, a number of papers have appeared that model these systems and test the or JE for these. FR... 

Hydrogen exchange of a protein under denaturing conditions can be described by the following simple two-state (folded/unfolded) model ... 

Ribosomal production of the unfolded state leads to amyloid fibril formation in the primitive situation. In the optimally evolved globular protein, the model native state can be formed and fibril formation can be overcome by one of the three cases. ... 

Large proteins, which act as catalysts for biological reactions, are known as enzymes. The tertiary structure of enzymes usually produces 3-dimensional pockets known as the active sites. The size and shape of the active site is specific for only a certain type of substrate, which is selectively converted to the product by the enzyme. This is often compared with a key fitting a lock (the lock and key model). The catalytic activity of the enzyme is destroyed by denaturation, which is the breakdown of the tertiary structure (i.e. the protein unfolds). This can be caused by a change in temperature or pH. 

Scheme 1. Kinetic model for the coupling between protein unfolding and prolyl isomerization.

Although much has been learned about the structure and function of Clp chaperones and their role in proteolysis, the mechanism of protein unfolding catalyzed by Clp ATPases and the mechanism of translocation of the unfolded proteins from Clp ATPases to partner proteases remain unsolved puzzles. However, models in which mechanical force is used to destabilize the structure of the substrate in a processive and directional manner are probable. It also seems likely that when ClpA ATPases are associated with proteases, unfolding is coupled to extrusion of the unfolded protein into the proteolytic cavity. In summary, it is anticipated that the large family of Clp ATPases will accomplish their many important cellular functions by similar mechanisms and what has been learned by studying the prokaryotic members reviewed here will shed a great deal of light on all members of the family. 

---