Relaxed complex scheme

Lin JH, Perryman AL, Schames JR, McCammon JA. 2002. Computational drug design accommodating receptor flexibility the relaxed complex scheme. J Am Chem Soc... 

Amaro RE, Baron R, McCammon JA (2008) An improved relaxed complex scheme for receptor flexibility in computer-aided drug design. J Comput Aided Mol Des 22(9) 693-705... 

Multilevel methods, where protein flexibility is accounted for at least in two independent stages of the docking protocol. This is the case of the relaxed complex scheme (RCS) [52, 53], in which an ensemble of unbound target structures is generated by MD and then used to dock a small chemical library... 

The relaxed-complex-scheme implements sampling irrformation in a straightforward way by taking the average of seoiing values of a hgand when docked to the individual periodically extracted corrformations. The developers of RCS observed in a first application that the most favorable scoring values resulted from non-native... 

A strong decrease in relaxivity (from 12.8mM-1s-1 to 2mM-1s-1) between pH 6 and 11 has been reported for a positively charged macrocyclic Gdm complex (Scheme 10), which was explained by the successive deprotonation of the coordinated water molecules.167 Luminescence lifetime measurements of a Yb111 analogue proved that the complex possesses three bound waters at pH 5.5. Above pH 11, a di-oxo-bridged dimer is formed that has no more bound water or OH groups. 

The products of thermal oxidation of polyethylene films can be characterized by C FTNMR furthermore, using the spin-lattice relaxation technique, quantitative estimates can be made of the oxidized functional groups. Observation of the development progress of the various functional groups leads to the postulation of hydroperoxides as the primary oxidation products, which undergo further transformations to the other derivatives in a complex scheme . 

The pH dependence of luminescence and relaxivity revealed that the complexes with europium, gadolinium and lanthanum might be used for MRI imaging. The concept was later verified by Frias et al. [8] by the use of structurally similar lanthanide complexes (Scheme 9). 

Lin, J. H., Perryman, A. L., Schames, J. R., and McCammon, J. A. (2003) The relaxed complex method accommodating receptor flexibility for drug design with an improved scoring scheme. Biopolymers 68,47-62. 

Scheme VIII has the form of Scheme II, so the relaxation time is given by Eq. (4-15)—appjirently. However, there is a difference between these two schemes in that L in Scheme VIII is also a participant in an acid-base equilibrium. The proton transfer is much more rapid than is the complex formation, so the acid-base system is considered to be at equilibrium throughout the complex formation. The experiment can be carried out by setting the total ligand concentration comparable to the total metal ion concentration, so that the solution is not buffered. As the base form L of the ligand undergoes coordination, the acid-base equilibrium shifts, thus changing the pH. This pH shift is detected by incorporating an acid-base indicator in the solution.

If two complexes coexist, there will be two relaxation times, and a treatment analogous to the analyses of Schemes III and IV is required. Table 4-2 gives a few rate constants for these reactions.The mechanism of such reactions is believed to consist of at least two steps, shown in simplified form in Scheme IX. 

An unusual pH dependence has been reported for the Gd111 complex of a tetraamide-based ligand with extended noncoordinating phosphonate side chains (Scheme 12).169,170 The relaxivity increases from pH 4 to 6, followed by a decrease until pH 8.5, then from pH 10.5 it increases again. The system, as well as isostructural lanthanide complexes, was characterized by various techniques such as 31P and 170 NMR and fluorescence measurements. The pH dependence could be attributed to protonation equilibria of the noncoordinating phosphonate groups, which can... 

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