Conformational microstates

Figure 1.6 Schematic representation of the changes in protein conformational microstate distribution that attend ligand (i.e., substrate, transition state, product and inhibitor) binding during enzyme catalysis. For each step of the reaction cycle, the distribution of conformational microstates is represented as a potential energy (PE) diagram.

Static In this case, the distribution of lifetimes is due to the existence of a continuum of conformational microstates, each characterized by its own lifetime. For time-resolved fluorometric detection of heterogeneity in this case, it is necessary for the rate of transition between such microstates to be slower than that of emission. 

Membrane bound conformations (microstates) vs. aqueous conformations... 

The additive may select particular conformational microstates that become fixed on drying ( imprinting ) ... 

Both the denaturation process in proteins and the melting transition (also referred to as the helix-to-coil transition) in nucleic acids have been modeled as a two-state transition, often referred to as the all-or-none or cooperative model. That is, the protein exists either in a completely folded or completely unfolded state, and the nucleic acid exists either as a fully ordered duplex or a fully dissociated monoplex. In both systems, the conformational flexibility, particularly in the high-temperature form, is great, so that numerous microstates associated with different conformers of the biopolymer are expected. However, the distinctions between the microstates are ignored and only the macrostates described earlier are considered. For small globular proteins and for some nucleic acid dissociation processes,11 the equilibrium between the two states can be represented as... 

Synthetic macromolecules do not in general exhibit relatively fixed conformations as do some biopolymers. Rather, each polymer molecule in solution is bombarded by the solvent molecules and, as a result of the rotations about bonds, scans through the huge range of accessible conformations. The chains assume neither their fully extended nor their fully compressed conformations since these are both highly ordered microstates. Instead, they adopt on average an intermediate conformation, usually referred to as a random coil 62... 

Calculation of entropies of both types is straightforward and efficient because simulations are not required. This allows one to study the conformational stability of many localized microstates of the same molecule by comparison of their harmonic free energies. However, the method is limited only to models of macromolecules in vacuum. 

Finally, it should be pointed out that because the transition probabilities are calculated in the LS method from the existing conformations and not from the future ones, the method is suited to handle a wide microstate that is defined on a limited region of conformational space (e.g., an a-helical... 

We conclude that CD and NMR methods, if applied with care to ensure maximum accuracy, do indeed measure the same equilibrium, most likely that between a right-handed single-helical stacked conformation and an assenr bly of unstacked microstates. Our combined NMR and CD data definitely rule out the presence of lefthanded (base-base overlapping) stacks in pu-py dimers in relative amounts large enough to cause the observed up-field shifts of U2 and A3 (24), or the downfield shifts of AS and AS" (21). If a left-handed (u4,u+) stacked species occurs in pu-py dimers, it must exist as partner in the blend of microstates. 

For the four-bead chain, there is one compact conformation and four open conformations (see Figure 10.1), so the density of states is W(0) = 1 and W(fo) = 4. Since W is the number of microstates per level, the partition function can be expressed as a sum over the two levels (open and compact, in this case), rather than over the five microstates,... 

How does the population of collapsed conformations change as the temperature is changed We focus here on the two macrostates, open and compact, rather than on the individual microstates, so the partition function for this... 

In this model which is applicable only to sequences (GQ - (GC) and (GT) (AQ the polynucleotide is considered as a homopolymer of dinucleotides GC and GT respectively. The energy of a microstate (counted off the energy of B-DNA) in which m nucleotides acquire the Z-conformation is ... 

Even at high temperature, MD simulations with explicit solvent are computationally too expensive to provide meaningful estimates of the conformational entropy of various dominant conformations or microstates. " Approximate entropy values can be obtained on the basis of harmonic or quasiharmonic approximations, or through the use of the more recent local states method. However, while accounting for the conformational entropy, these methods are at present restricted to the analysis of isolated molecules. It is very... 

Third, generalized equations of motion have been proposed to sample arbitrary (i.e., not necessarily canonical) probability distributions [134, 135, 136, 137]. Such methods can be used, e.g., to optimize the efficiency of conformational searches [134, 135, 137] or for generating Tsallis distributions of microstates [136]. 

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