Native proteins, folding dynamics

The tolerance of the protein folding process to noise in the interaction parameters and sequence modifications [93] was also studied using a 3x3x4 target structure [94]. The conclusions were in agreement with the qualitative picture of real protein folding dynamics and thermodynamics [93]. Such studies are important because they may provide some insights into how specific the protein sequence has to be in order to maintain the structural uniqueness of the native conformation. 

Gilmanshin R., Williams S., Callender R. H., Woodruff W. H. and Dyer R. B. Fast events in protein folding relaxation dynamics of secondary and tertiary structure in native apomyoglobin. Proc. Natl. Acad. Sci., USA (1997) 94(8) 3709-3713. 

Faisca PFN, da Gama MMT (2005) Native geometry and the dynamics of protein folding. Biophys. Chem. 115 169-175... 

Proteins. The questions, What kinds of mechanisms carry a protein into an unique native state and What is the best reaction coordinate to describe the dynamics of protein folding have been among the most intriguing subjects over the past decades in biological physics [35,36]. The process of protein folding may be interpreted as a normal Brownian process of a few collective... 

This approximate law holds for both native structure [22] and folding dynamics [2], In this regard, this wrapping motif may be regarded as a structural element that captures the basic component of energy transduction from hydrophobic association to structure formation. Furthermore, it implies that a fundamental constraint in protein architecture applicable to native structures applies also throughout the folding trajectory. 

Multidomain proteins may be viewed as conjugated proteins in which each domain may affect the folding dynamics and thermodynamic properties of its counterpart domain. Experimentally, the thermodynamics and kinetics of both isolated domains and conjugated constructs from several multidomain proteins were studied (a very detailed and fairly current report can be found in Reference [29]). A computational characterization of the mechanistic principles of the folding of multidomain proteins [33], utilizing native structure-based models, provides a reduced microscopic description of their folding, which in turn may enable the formulation of the forces involved in the interplay between neighboring domains. 

The protein folding problem - the ability to predict a protein fold from its sequence - is one of the major prizes in computational chemistry. Molecular dynamics simulations of solvated proteins is currently not a feasible approach to this problem. However, Duan and Kollman have shown that a 1 ps simulation on a small hydrated protein, here the 36 residue villin headpiece, is now possible using a massively parallel super computer.33 The native protein is estimated to fold in about 10-100 ps and so the simulation can only be used to study the early stages of protein folding. Nevertheless, starting from an extended structure the authors were able to observe hydrophobic collapse and secondary structure formation (helix 2 was well formed, helices 1 and 3 were partially formed and the loop connecting helices 1 and 2 was also partially... 

Compared to natively folded proteins, compact denatured states ( MGs ) experience a modest increase in the number of water molecules in the hydration layer, and a slightly smaller perturbation of hydration water dynamics. Soluble protein-water dynamical coupling has been elucidated by simultaneous examination of transitions in protein and water dynamics as a function of temperature. Hydrated proteins at room temperature exhibit liquid-like motion on the subnanosecond timescale and behave like glasses at low temperature. The dynamical (or glass) transition between the low-temperature glassy state and room-temperature liquid-like state plays an important role in energy flow processes in proteins (see Ref [86] and Chapters 7 and 11). 

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