Ligand-protein contacts

Ligand-Protein Interactions The energy of formation of ligand-protein contacts can be computed as a sum of non-bonded (Lennard-Jones and electrostatic) terms similar to those used in a molecular dynamics simulation. 

Ligand-protein contact (LPC) data describe putative surface interactions between the ligand and the site residues and predict whether they are energetically favourable or unfavourable [18,19], Putative hydrogen bonds are labelled as backbone, functional group donors or acceptors or amphiprotic. Putative hydrogen bonds with bond lengths less than or equal to 3.5A are accepted and considered in this analysis. 

The DrugScore function by Gohlke et al. (226) is based on roughly the same formalism, albeit with several differences in the derivation that lead to different potential forms. Most notably, the statistical distance distributions p (r)/p for the individual atom pairs ij are divided by a common reference state that is taken as the average over the distance distributions of all atom pairs p(r) = 22 p (r)fij. To consider only direct ligand-protein contacts, the upper sample radius has been set to 6 A. At this distance, no further atoms (e.g., of a water molecule) can mediate a protein-ligand interaction. The individual potentials have the form... 

McBryant, S.J., E.E. Baird, J.W. Trauger, P.B. Dervan, and J.M. Gotteseeld. Minor groove DNA-protein contacts upstream of a tRNA gene detected with a synthetic DNA binding ligand. /. Mol. Biol. 1999, 286, 973-981. 

On the other hand, consider the probability that a particular ligand type is making a certain number of protein contacts. This is given by... 

Fig. 4. Protein contact surface representation of the beta-catenin/Tcf4 protein compiex interface near Tcf4 (D16). The QSURF coior-coded surface highiight two protein micro-cavities that anchor the ligand PNU-74654 at two opposite sites orange dot circle) involving a methyl-furan moiety and a benzene ring.

For evaluation of efficiency of medical sorbents, the issue of their deliganding properties, i.e. an ability to withdraw toxic protein bound compounds (ligands) is of great importance. If a sorbent possesses strong deliganding capability as, for example, some types of modem carbon hemosorbents do [11,12], then after contact with such an adsorbent, the ratio of molar concentrations of ligand - protein carrier (M /Mp) decreases, i.e. the transport protein transforms into a more purified state than it was initially (Table 21.3). 

The 2.0 A electron density map of carboxypeptidase A shows three zinc-protein contacts (91). The ligands have been identified as histidine-69, glutamic acid-72 and histidine-196 (91, 101), where the numbers indicate the positions of the residues in the sequence counted from the N-terminal end. The geometry of the complex is irregular but resembles a distorted tetrahedron with an open position directed towards the active site pocket, and presumably occupied by water in the resting enzyme (91). The similarity with the tentative structure of the metal-binding site in carbonic anhydrase is striking. 

Catabolite repression is a two-part system. The first component is the small-molecule regulator, cyclic AMP. Glucose decreases cyclic AMP synthesis. The second component is cyclic AMP binding protein, CAP. CAP binds cAMP and thereby helps RNA polymerase bind to the promoter. When bound to cAMP, CAP binds to a sequence at the 5 end of the lac promoter. CAP binding bends the DNA, allowing protein-protein contact between CAP and polymerase. It therefore behaves in the opposite manner of repressor. Repressor (LacI) binds to operator DNA only in the absence of its small-molecule ligand, while CAP binds to promoter DNA in the presence of its small-molecule ligand. 

Skin sensitization tests assess the ability of chemicals to affect the immune system, such that a second contact causes a more severe reaction than the first. The antigen involved is presumed to be formed in the bonding of the chemical to body proteins. The antibodies that form to this ligand-protein complex give rise to an allergic reaction with subsequent exposure. 

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