Ligand-protein systems

Study Ligand-Protein Docking for information about drug design. Review movies showing interactions with a variety of ligand-protein systems. 

The affinity of interactions can be calculated in a number of ways. One example is the force field method to calculate the free energy of binding for the ligand-protein system before and after the docking, as given by the equation ... 

Lowry, O.H. Rosebrough, N.J. Farr, A.L. and Randall, R.J. Protein measurement with folin phenol reagent. J Biol Chem 193 265-275, 1951. Munson, P.J.. and Rodbard, D. LIGAND A versatile computerized approach for characterization of ligand binding systems. Anal Biochem 107 220-237. 1980. 

The active-site model (and the ONIOM model system) includes Fe, one aspartate and two histidine ligands, a water ligand and selected parts of the substrate (see Figure 2-6). The 2-histidine-1-carboxylate ligand theme is shared by several other non-heme iron enzymes [59], For the protein system, we used two different... 

The ONIOM protein system contains the substrate, methylmalonyl-CoA, bound to the active site, the cofactor (AdoCbl) and all amino acids within a 15-A radius from the cobalt atom. The active-site selection contains a truncated AdoCbl and the imidazole ring of its lower ligand. The QM part was calculated using the BP86 functional [31, 72] because it gives better agreement with experimental Co—C bond energies [73, 74], This a different choice of functional compared to the other studies in the present review. 

As examples. Table 8 records some observations on d—d and charge transfer absorption bands in metal/protein systems. The examination of the spectrum of cobalt carbonic anhydrase (d—d) and of iron conalbumin (charge-transfer) permitted a prediction of the ligands from the protein to the metal. The predictions have now been substantiated by other methods. 

Derrick studied the interaction of L-tryptophan and ibuprofen with human serum albumin (HSA),74 which is an abundant transport blood protein capable of binding efficiently several species.75 They acquired 1H NMR spectra of L-Tryptophan-HSA system for different ligand protein molar ratios, that is 3 1, 5 1, 7 1 and 10 1. The aromatic resonances of L-Tryptophan are difficult to be observed due to the overlap with HSA signals, even at 10 1 molar ratio, so that the spectral subtraction was performed. D values of L-Tryptophan were calculated by integration of the subtracted spectra and were in good agreement with those predicted by computer simulations. In the case of ibuprofen, only for 140 1 molar ratio, the resonances of ibuprofen are clearly visible also in this case, the... 

Licitra, E. J., and Liu, J. O. (1996). A three-hybrid system for detecting small ligand—protein receptor interactions. Proc. Natl. Acad. Sci. USA 93, 12817—12821. 

Nanoparticle surface modification is of tremendous importance to prevent nanoparticle aggregation prior to injection, decrease the toxicity, and increase the solubility and the biocompatibility in a living system [20]. Imaging studies in mice clearly show that QD surface coatings alter the disposition and pharmacokinetic properties of the nanoparticles. The key factors in surface modifications include the use of proper solvents and chemicals or biomolecules used for the attachment of the drug, targeting ligands, proteins, peptides, nucleic acids etc. for their site-specific biomedical applications. The functionalized or capped nanoparticles should be preferably dispersible in aqueous media. 

Measurements of the proximal histidine-iron stretching frequency by Resonance Raman spectroscopy revealed that this bond is very weak in relation to other heme protein systems (vFe.His = 204 cm-1) (130). Formation of the sGC-NO complex labilizes this ligand resulting in the formation of a 5-coordinate high spin iron(II) complex, and the conformational change responsible for the several hundred-fold increase in catalytic activity (126,129,130). 

Because metal substitution and ligand variation affect ET kinetics without perturbing the structure of the ET complex, such changes were used to probe mechanistic aspects of ET. The data show that both photoinitiated and thermal ET are direct processes. The measurements of k( in the [ZnP, Fe (H20)P] hybrids provided the first detection of ET tuimelling in a structurally-defined protein system. 

The third principle observed in designed heme protein systems is that local electrostatics can have a significant impact on the measured heme reduction potential values. The initial heme protein maquette work demonstrated the elevation of heme reduction potentials using local charges, based on both amino acids, Arg+, and adjacent oxidized hemes, [Fe(III)(por)]+. In the case of heme-amino acid electrostatic interactions, Robertson et al. (127) concluded that the presence of an arginine four amino acids removed from the histidine ligand, -HEERL-,... 

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