Structure difference between conformers

For more substantial structural differences between conformers involving multiple dihedral angles, importance sampling or the perturbation procedure are probably the best approaches using a one-dimensional reaction path with concerted variations in the angles. Obtaining even a complete two-dimensional map for the solvent effect, e.g. is computationally too demanding. Adequate simulations... 

The second application of the CFTI approach described here involves calculations of the free energy differences between conformers of the linear form of the opioid pentapeptide DPDPE in aqueous solution [9, 10]. DPDPE (Tyr-D-Pen-Gly-Phe-D-Pen, where D-Pen is the D isomer of /3,/3-dimethylcysteine) and other opioids are an interesting class of biologically active peptides which exhibit a strong correlation between conformation and affinity and selectivity for different receptors. The cyclic form of DPDPE contains a disulfide bond constraint, and is a highly specific S opioid [llj. Our simulations provide information on the cost of pre-organizing the linear peptide from its stable solution structure to a cyclic-like precursor for disulfide bond formation. Such... 

The free energy differences obtained from our constrained simulations refer to strictly specified states, defined by single points in the 14-dimensional dihedral space. Standard concepts of a molecular conformation include some region, or volume in that space, explored by thermal fluctuations around a transient equilibrium structure. To obtain the free energy differences between conformers of the unconstrained peptide, a correction for the thermodynamic state is needed. The volume of explored conformational space may be estimated from the covariance matrix of the coordinates of interest, = ((Ci [13, lOj. For each of the four selected conform-... 

The Ca -ATPase has been crystallized in both conformations [119,152-155]. The two crystal forms are quite different [10,88-93,156-161], suggesting significant differences between the interactions of Ca -ATPase in the Ei and E2 conformations. Since the Ei-E2-transition does not involve changes in the circular dichroism spectrum of the Ca -ATPase [162], the structural differences between the two states presumably arise by hinge-like or sliding motions of domains rather than by a rearrangement of the secondary structure of the protein. 

The intramolecular distances measured at room temperature with the AEDANS FITC pair were similar in the Ca2Ei and E2V states [297]. Ca and lanthanides are expected to stabilize the Ej conformation of the Ca -ATPase, since they induce a similar crystal form of Ca -ATPase [119,157] and have similar effects on the tryptophan fluorescence [151] and on the trypsin sensitivity of Ca -ATPase [119,120]. It is also likely that the vanadate-stabilized E2V state is similar to the p2 P state stabilized by Pi [418]. Therefore the absence of significant difference in the resonance energy transfer distances between the two states implies that the structural differences between the two conformations at sites recorded by currently available probes, fall within the considerable error of resonance energy transfer measurements. Even if these distances would vary by as much as 5 A the difference between the two conformations could not be established reliably. 

Fig. 4. The molecular structure, determined by solution NMR (James et al., 1997), of Syrian hamster 90-231 (SHa90-231) prion with ball-and-stick representation of the HI domain (SHal09-122 MKHMAGAAAAGAW). Note that two short /(-chains (SI, S2) nearly stack in the hydrogen-bonding direction. If the palindromic polyalanine region was also in a /(-conformation, there would be a three-stranded /(-sheet. The structural difference between PrPc and PrPSc is in the 90-145 domain. [Model drawn using MOLSCRIPT (Kraulis, 1991)].

The structural differences between the R- and T-form are strongest at the interface between the dimers and impact heavily the binding site for fructose-6-P. At the binding site for the second substrate, ATP, there are only minor structural differences between the two conformations. Overall, the transition from R- to T-form is accompanied by a rotation of the two dimers aroimd the small interface the large contact surface within a dimer remains relatively imchanged. 

The switch fimction of the a-subunit of the heterotrimeric G-proteins is foimded on the change between an active G -GTP confirmation and an inactive Ga-GDP conformation. The structural difference between the two conformations was explained for the transducin, G, , by crystallization and structural characterization of the inactive GDP form and the active GTPyS form (Lambright et al., 1994). The structures of both forms of Gt, are shown in Fig. 5.19. 

The most relevant structural difference between the a and p monomers is located in the loop S9-S10, which is 8 residues longer in a-tub than in p-tub owing to an insertion. In the a-subunit, the long S9-S10 loop stabilizes the M loop. In the P-subunit, the equivalent position is occupied by the PTX binding site. This suggests that PTX mimics the 8-residue insertion of the a-subunit loop. In fact, the atomic model shows that the PTX molecule acts as a linker between helix H7 and the M loop, possibly stabilizing an M loop conformation that favors the lateral interprotofilament interaction and contributes to MT stabilization [24, 25], Both side chains and the baccatin core of PTX participate in these interactions [25],... 

Our present result showed that the structure differences between the Pr and Pfr forms are both in the C15=C16 rotation from Z- to E-conformation and in the C14-C15 rotation from anti- to syn-conformation. Therefore, ZZEasa isomer is a possible candidate for the lumi-R or meta-Ra forms. The calculated excitation energy for ZZEasa isomer was 1.71 eV, which was 0.02 eV smaller than that of ZZZasa isomer, Pr form. The result suggested that lumi-R and meta-Ra could have ZZEasa structure as a basic skeleton. 

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