Automatic epitope recognition in proteins oriented to the system for macromolecular interaction assessment MIAX.

In the present work we evaluate the performance of an algorithm for the automatic recognition of binding sites in proteins as well as in other macromolecules whose interactions are involved in many cellular and physiological processes. The algorithm is a combination of an unsupervised learning algorithm - based on Kohonen self organizing maps - to characterize the properties of patches of protein solvent accessible surfaces and a filtering algorithm to establish both the physical boundaries of the patches as well as the level of contribution of different and distant atoms involved in the interaction. We have found that the algorithm performs extremely well in a set of randomly selected protein complexes for which the interaction interfaces are extracted and compared with the results of the algorithm. A statistical evaluation of the algorithm is additionally performed by analysis of the degree of hydrophobicity and hydrophilicity of the output patches and comparison with that of the observed interface constituent amino acids.

A synthetic peptide of human apoprotein E with antibacterial activity.

In recent years, several endogenous mammalian antibacterial peptides have been described. An amphipathic cationicalpha-helix is a common feature in many cases; therefore, other peptides with this characteristic might also possess antibiotic activity. In fact, a 30-mer peptide of apoprotein E 133-162 (LRVRLASHLRKLRKRLLRDADDLQKRLAVY) was found to have antibiotic activity comparable to those of a classic antibiotic (Gentamicin) and a neutrophil-derived antibiotic peptide (CAP18). Calculation of cationicity, hydrophobicity, and hydrophobic moment and the helical wheel diagram of apoprotein E 133-162 revealed close similarities to CAP18.

MIAX: a system for assessment of macromolecular interaction. 3) A parallel hybrid GA for flexible protein docking.

We propose a parallel hybrid genetic algorithm for flexible protein-protein docking in order to improve the conventional rigid-body models to manipulate protein-protein interactions. The proposed hybrid algorithm is a combination of an evolutionary algorithm with a simulated annealing one, yielding a powerful protein-complex conformation-searching engine. Parallelization of the procedure makes possible to reach high algorithm performance, in both, execution times and size of treated monomers and complexes. Knowledge on side chain flexibility is extracted by means of an exhaustive analysis of crystallographic data on proteins and protein complexes. Results demonstrate the competency of the algorithm since comparison of calculated and crystallographic data accounts for a maximum of 2.5A in RMS difference, including side chain conformation. The system allows routine analysis of this fundamental molecular biology problem important to elucidate bio-macromolecular function in biophysical and biochemical mechanisms involving molecular recognition and interaction, yielding simultaneously clues for designing new proteins and enzymes directed to different purposes.

Antibacterial activity of multiple antigen peptides homologous to a loop region in human lactoferrin.

An 11-residue peptide (FQWQRNMRKVR) homologous to just over half the loop region of human lactoferricin is thought to be responsible for antimicrobial properties of human lactoferricin. Multiple antigen peptides (MAP) of the 11-residue peptide exerted significant antibacterial effects against a broad spectrum of bacteria including MRSA. More than eight branching was favourable for increasing its antibacterial activity. Our report shows a novel possibility for MAP to increase the activity of antibiotic peptides other than simply to stimulate antibody production, as reported so far.

Inhibition of complement-mediated immune hemolysis by peptides derived from the constant domain of immunoglobulin.

High-dose administration of intravenous immunoglobulin is reported to be useful for inhibiting complement-dependent immune cytolysis. We have found that, among the proposed C1q-binding sites of the Fc portion of human IgG1, only residues 282-292 inhibited pig red blood cell lysis by human serum. Moreover, a hexadecemeric multiple antigen peptide of residues 282-292 from IgG showed significantly greater activity in suppressing complement-mediated immune cytolysis and can be used in place of high-dose intravenous immunoglobulin, which is extracted from donors and thus is expensive.

A new approach to the automatic identification of candidates for ligand receptor sites in proteins: (I). Search for pocket regions.

The work presented here is aimed at the topographical analysis of localized regions of receptor proteins leading to the identification of pocket areas (superficial depressions or internal cavities), which may play the role of receptor sites. An algorithm is described that yields complete information about the position of each cavity or superficial depression relative to any point of the protein molecules, as well as detailed information on the atoms constituting it. The applicability of this algorithm to the automatic identification of candidate receptor sites in a receptor protein is also discussed using the typical receptor structure dihydrofolate reductase-methotrexate complex.