ABSTRACT
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.
Subject(s)
Algorithms , Proteins/chemistry , Proteins/immunology , Binding Sites , Computational Biology , Epitopes , Macromolecular Substances , Models, Molecular , Proteins/metabolismABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides , Apolipoproteins E/chemistry , Apolipoproteins E/pharmacology , Bacteria/drug effects , Peptide Fragments/pharmacology , Amino Acid Sequence , Carrier Proteins/pharmacology , Cathelicidins , Drug Resistance, Multiple , Escherichia coli/drug effects , Gentamicins/pharmacology , Humans , Microbial Sensitivity Tests , Molecular Sequence Data , Peptide Fragments/chemical synthesis , Peptide Fragments/chemistry , Protein Structure, Secondary , Pseudomonas aeruginosa/drug effects , Salmonella/drug effects , Staphylococcus aureus/drug effectsABSTRACT
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.
Subject(s)
Algorithms , Proteins/chemistry , Biological Evolution , Computational Biology , Computer Simulation , Macromolecular Substances , Models, Genetic , Models, Molecular , Mutation , Protein Binding , Protein Conformation , Proteins/genetics , Proteins/metabolismABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antigens/pharmacology , Lactoferrin/pharmacology , Peptide Fragments/pharmacology , Peptides/pharmacology , Amino Acid Sequence , Anti-Bacterial Agents/chemistry , Apoproteins/chemistry , Escherichia coli/drug effects , Humans , Lactoferrin/chemistry , Models, Molecular , Molecular Sequence Data , Peptide Fragments/chemical synthesis , Peptides/chemical synthesis , Protein Conformation , Protein Structure, Secondary , Pseudomonas aeruginosa/drug effects , Salmonella/drug effects , Staphylococcus aureus/drug effectsABSTRACT
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.
Subject(s)
Complement System Proteins/immunology , Hemolysis , Immunoglobulin Constant Regions/physiology , Immunoglobulin G/physiology , Peptide Fragments/physiology , Complement C1q/metabolism , HumansABSTRACT
Para la elección del calor de la resina siempre debe realizarse en el diente mojado, porque el diente seco cambia temporalmente el matiz del esmalte. Se debe de preferencia realizar el tallado de la cara oclusal de la restauración con piedras de diamante accionadas a baja velocidad. No se debe realizar el grábado ácido del ionomero vitrio. Recomendar al paciente tener una buena higiene bucal una vez colocado. El material de restauración. Alcanzar un buen pulido y fotopolomerirización del material restaurado. El material de restauración y de impresión se debe mantener refrigerado. Controlar o verificar la intensidad de la luz halógena periodicamente. No utilizar ningún material despues de la fecha de su vencimiento. Para la preparación o manipulación de las siliconas no debe usarse guantes de látex
Subject(s)
Male , Female , Humans , Child , Adult , Composite Resins/classification , Composite Resins/standards , Composite Resins/chemistryABSTRACT
In order to detect periods of synchronous gene expressions during embryogenesis of Oncorhynchus masou (Yamame), we analyzed the peptide constituents of the embryos by means of two-dimensional electrophoresis. New kinds of peptides were mainly detected in three periods, i.e. between the 12th and 13th day, between the 20th and 21st day, and between the 30th and 31st day after fertilization. Hatching occurred between the 34th and 37th day. These indicate that these three periods, which corespond to (1) the shifting stage from maternal to nuclear events in gene expression, (2) the development of external organs such as fins, and (3) the preparative stage for hatching, respectively, may be critical stages in gene expression.
Subject(s)
Gene Expression Regulation, Developmental , Oncorhynchus/genetics , Animals , Electrophoresis, Gel, Two-Dimensional , Oncorhynchus/embryologyABSTRACT
This paper investigates the V beta usage of lymph node cells from mice immunized with TNP and of cell lines made from them. In cell lines stimulated weekly with TNP in vitro for 1 month, about 87% of the cells were V beta 8+ and further analysis showed that these cells were actually V beta 8.2+. This was also true for the cells that proliferated in lymph nodes in response to TNP 4 days after primary immunization, i.e. proliferation occurred mainly in the V beta 8+, and in particular in the V beta 8.2+, population while much less proliferation occurred when the V beta 8- or V beta 8.2- T-cell populations are used. This was not due to non-specific damage during separation, as the response to concanavalin A and alloantigen was intact. In a separate series of experiments, mice were acutely depleted of V beta 8+ T cells by treatment with F23.1 or a control monoclonal antibody (mAb) in vivo given before immunization. Treatment with the relevant mAb virtually abolished the response to TNP. In contrast, SJL mice, which lack the gene segment coding for the V beta 8 family and several other V beta chains, made a normal proliferative and delayed-type hypersensitivity (DTH) response to TNP. This poses the problem, which may be important in the study of the T-cell repertoire, of why acute removal of V beta 8+ T cells, which are dominantly used in the response to TNP, does not allow T cells using other chains to substitute in the response, while the absence of this population over a long period of time, because of a deletion in the genome, allows the use of T cells bearing other V beta chains.
Subject(s)
Receptors, Antigen, T-Cell, alpha-beta , Receptors, Antigen, T-Cell/genetics , T-Lymphocytes/immunology , Trinitrobenzenes/immunology , Animals , Antibodies, Monoclonal/immunology , Cell Division/immunology , Cell Line , Dermatitis, Contact/immunology , Lymph Nodes/immunology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred CBA , Mice, Inbred Strains , Receptors, Antigen, T-Cell/immunologyABSTRACT
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.
