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Results for “computational design”

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At least 1,261 records · Page 70Linked to original sources
PubMed2000

Design of dimerization inhibitors of HIV-1 aspartic proteinase: a computer-based combinatorial approach.

Inhibition of dimerization to the active form of the HIV-1 aspartic proteinase (HIV-1 PR) may be a way to decrease the probability of escape mutations for this viral protein. The Multiple Copy Simultaneous Search (MCSS) methodology was used to generate functionality maps for the dimerization interface of HIV-1 PR. The positions of the MCSS minima of 19 organic fragments, once postprocessed to take into account solvation effects, are in good agreement with experimental data on peptides that bind to the interface. The MCSS minima combined with an approach for computational combinatorial ligand design yielded a set of modified HIV-1 PR C-terminal peptides that are similar to known nanomolar inhibitors of HIV-1 PR dimerization. A number of N-substituted 2,5-diketopiperazines are predicted to be potential dimerization inhibitors of HIV-1 PR.

Aspartic Acid Endopeptidases↗
PubMed2006

Computational methods in drug design: modeling G protein-coupled receptor monomers, dimers, and oligomers.

G protein-coupled receptors (GPCRs) are membrane proteins that serve as very important links through which cellular signal transduction mechanisms are activated. Many vital physiological events such as sensory perception, immune defense, cell communication, chemotaxis, and neurotransmission are mediated by GPCRs. Not surprisingly, GPCRs are major targets for drug development today. Most modeling studies in the GPCR field have focused upon the creation of a model of a single GPCR (ie, a GPCR monomer) based upon the crystal structure of the Class A GPCR, rhodopsin. However, the emerging concept of GPCR dimerization has challenged our notions of the monomeric GPCR as functional unit. Recent work has shown not only that many GPCRs exist as homo- and heterodimers but also that GPCR oligomeric assembly may have important functional roles. This review focuses first on methodology for the creation of monomeric GPCR models. Special emphasis is given to the identification of localized regions where the structure of a GPCR may diverge from that of bovine rhodopsin. The review then focuses on GPCR dimers and oligomers and the bioinformatics methods available for identifying homo- and heterodimer interfaces.

Amino Acid Sequence↗
PubMed2005

Computational studies and drug design for HIV-1 reverse transcriptase inhibitors of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs.

Molecular docking and molecular dynamics simulation were applied to study the binding mode of 3',4'-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogs anti-HIV inhibitors with HIV-1 RT. The results suggest that there is a strong hydrogen bond between DCK O16 and NH of Lys101, and that DCK analogues might act similarly as other types of HIV-1 RT inhibitors. The investigation about drug resistance for DCK shows no remarkable influence on the most frequently observed mutation K103N of HIV-1 RT. Based on the proposed mechanism, some new structures were designed and predicted by a SVM model. All compounds exhibited potent inhibitory activities against HIV replication in H9 lymphocytes with EC50 values lower than 1.95 microM. The rationality of the method was validated by experimental results.

Camphor↗
PubMed1999

Design and implementation of computational systems based on programmed mutagenesis.

In a new system for DNA computation called programmed mutagenesis, DNA strands are rewritten according to 'rules' that are sequence specific. In a programmed mutagenesis reaction DNA sequences undergo programmed changes, and these changes are implemented by an in-vitro mutagenesis system that is based on thermal cycling the rewriting reaction. We describe experimental results that demonstrate the key aspects of programmed mutagenesis. These results include the creation of full-length product DNA molecules that have embedded rewriting, the ability for later sequence changes to depend on earlier sequence changes, and the ability for multiple oligonucleotides to be active in close proximity on a template sequence. We also discuss the application of programmed mutagenesis to computational problems.

Animals↗
PubMed1998

Computational fluid dynamic analyses to establish design process of centrifugal blood pumps.

To establish quantitative, efficient design theories for centrifugal blood pumps, computational fluid dynamics (CFD) analyses were compared to the results of flow visualization tests and hemolysis tests, mainly on the Nikkiso centrifugal blood pump. The results turned out to coincide in the velocity vector plots. CFD analysis revealed that the smaller the gap is, the greater the shear stress becomes. This tendency becomes even greater with a radial gap change. Hemolysis study also indicated that the smaller the gap is, the greater the hemolysis. CFD analysis in comparison with hemolysis tests could be a useful index for developing blood pumps in the future.

Biomechanical Phenomena↗
PubMed1997

Demonstration of a word design strategy for DNA computing on surfaces.

A strategy for DNA computing on surfaces using linked sets of 'DNA words' that are short oligonucleotides (16mers) is proposed. The 16mer words have the format 5'-FFFFvvvvvvvvFFFF-3' in which 4-8 bits of data are stored in 8 variable ('v') base locations, and the remaining fixed ('F') base locations are used as a word label. Using a template and map strategy, a set of 108 8mers each of which possesses at least a 4 base mismatch with the complements to all the other members of the set (4bm complements) are identified for use as a variable base sequence set. In addition, sets of 4 and 12 word labels of the form ABCD....DCBA that are respectively 8bm and 6bm complements with each other are identified. The 16mers are chosen to have a G/C content of 50% in order to make the thermodynamic stability of the perfectly matched hybridized DNA duplexes similar; a simple pairwise additive method is used to estimate the perfect match and mismatch hybridization thermodynamics. A series of preliminary experiments are presented that use small arrays of 16mers attached to chemically modified gold surfaces and fluorescently labeled complements to study the hybridization adsorption and enzymatic manipulation of the oligonucleotides.

Base Sequence↗
PubMedDate not supplied

A design model for computer-based guideline implementation based on information management services.

Clinical practice guidelines must be implemented effectively if they are to influence the behavior of clinicians. The authors describe a model for computer-based guideline implementation that identifies eight information management services needed to integrate guideline-based decision support with clinical workflow. Recommendation services determine appropriate activities in specific clinical circumstances. Documentation services involve data capture. Registration services integrate demographic and administrative data. Explanation services enhance the credibility of automated recommendations by providing supportive evidence and rating the quality of evidence. Calculation services measure time intervals, suggest medication dosages, and perform other computational tasks. Communication services employ standards for information transfer and provide data security. Effective presentation services facilitate understanding of complex data, clarify trends, and format written materials (including prescriptions) for patients. Aggregation services associate outcomes with specific guideline interventions. The authors provide examples of the eight services that make up the model from five evidence-based practice parameters developed by the American Academy of Pediatrics.

Decision Support Systems, Clinical↗
PubMed1994

Estimation of growth hormone secretory patterns in children with use of a numerical deconvolution technique: experimental design with use of computer simulation.

Growth hormone (GH) secretion rates were estimated from 24-hour plasma GH concentration profiles using a model-based numerical deconvolution method. The basic kinetic parameters describing GH distribution and elimination were obtained from studies using single intravenous injections in GH-deficient children. Computer simulation techniques were used to produce 24-hour GH secretion profiles, which could serve as reference curves for analysis of the impact of certain practical aspects of the estimation of GH secretion, such as the method of blood sampling (discrete or integrated), sampling frequency and analytical errors. The results show that sampling intervals of 20 min are acceptable even in the presence of analytical errors, and that with this sampling interval, discrete blood sampling does not seem to be preferable to continuous withdrawal of blood.

Blood Specimen Collection↗
PubMed1999

North American approach to smoke management.

The term smoke is used to mean the airborne products of combustion and air that is mixed with those products. A smoke control system is used to mean a system intended to manage smoke by pressurisation, and smoke management system is a broader term that includes systems that use any combination of compartmentation, dilution, air flow, pressurization or buoyancy. Smoke control systems include zoned smoke control, pressurized stairwells, and elevator smoke control. Over the past few decades there have been a number of full scale fire tests that demonstrate that pressure differences can prevent smoke migration from the low pressure side to the high pressure side of a barrier. While there are equations that can be used for smoke control design, network computer models can account for the effects of complex building leakage paths. For simplicity the term atrium was used in this paper in a generic sense to mean almost any large space (such as arcades, sports arenas, and exhibition halls). In North America most atria rely on sprinkler protection for spaces connected to the atrium and fan powered exhaust at or near the top of the atrium. Because the ability of sprinklers to suppress fires in spaces with ceilings higher than about 11m is limited, smoke exhaust is especially important for fires that start in the atrium. Equations and computer zone models can be used for the design of atrium exhaust systems. When these approaches are inappropriate, CFD modelling or physical modelling can be used.

Elevators and Escalators↗
PubMed2001

[Computer-assisted audiometry].

A computer audiometer has been designed on the computer using program "Audiometry". No special devices are needed. This computer audiometric complex can perform all kinds of behavioral audiometry: tonal threshold, suprathreshold, speech and in a free sound field.

Audiometry, Pure-Tone↗
PubMedDate not supplied

Computer supported studies on design and evaluation of solid dispersions of carbamazepine.

The main advantages of solid dispersions (the drug could be maintained in a bioavailable form, dosage reduction and cleaner manufacturing conditions) provide scope for the continued interest in field. Additionally, their use in providing a sustained or controlled release of drugs has only been tentatively examined. In the present study, Carbamazepine has been used to develop a dosage form which will provide a booster amount followed by sustained release of the drug for effective control of epileptic seizures while keeping the serum level of the drug at minimum. Enteric polymers CAP and CAT have been used to retard the release till the formulation reaches the intestine. Either individually or combined fractions of the formulations may be used in the therapy of epilepsy.

Anticonvulsants↗