Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “computational design”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed2004

[KiBank: a database for computer-aided drug design based on protein-chemical interaction analysis].

KiBank is a database for computer-aided drug design and consists of binding affinities and chemical and target protein structures. Each chemical or protein structure with hydrogen atoms added was optimized by energy minimization and stored in PDB or MDL MOL file format, so that the structural data can be directly used for in silico binding studies. To describe the extent of inhibition, the inhibition constant (K(i)) value is used to simplify comparisons of strengths among chemical-protein bindings. As of April 2004, KiBank contained 142 proteins, over 5000 chemicals, and over 6000 binding affinity values that were published in peer-reviewed journals. The binding affinity values are currently mostly for membrane and nuclear receptors but are soon being expanded to other drug targets. KiBank is updated daily and can be accessed on the Web at http://kibank.iis.u-tokyo.ac.jp/at no charge.

Computer-Aided Design↗
PubMed2006

Distance based algorithms for small biomolecule classification and structural similarity search.

MOTIVATION: Structural similarity search among small molecules is a standard tool used in molecular classification and in-silico drug discovery. The effectiveness of this general approach depends on how well the following problems are addressed. The notion of similarity should be chosen for providing the highest level of discrimination of compounds wrt the bioactivity of interest. The data structure for performing search should be very efficient as the molecular databases of interest include several millions of compounds. RESULTS: In this paper we focus on the k-nearest-neighbor search method, which, until recently was not considered for small molecule classification. The few recent applications of k-nn to compound classification focus on selecting the most relevant set of chemical descriptors which are then compared under standard Minkowski distance L(p). Here we show how to computationally design the optimal weighted Minkowski distance wL(p) for maximizing the discrimination between active and inactive compounds wrt bioactivities of interest. We then show how to construct pruning based k-nn search data structures for any wL(p) distance that minimizes similarity search time. The accuracy achieved by our classifier is better than the alternative LDA and MLR approaches and is comparable to the ANN methods. In terms of running time, our classifier is considerably faster than the ANN approach especially when large data sets are used. Furthermore, our classifier quantifies the level of bioactivity rather than returning a binary decision and thus is more informative than the ANN approach.

Algorithms↗
PubMed2026

Toward life with a 19-amino acid alphabet through generative artificial intelligence design.

Because all known living organisms are made from at least 20 canonical amino acids, the feasibility of life using a more simplified alphabet remains unclear. In this work, we leveraged computational design and synthetic biology to explore building a cell from a 19-amino acid alphabet. Initial analyses suggested that isoleucine (Ile) may be dispensable, which we confirmed by directly replacing Ile residues in essential proteins in Escherichia coli. Critically, protein language models and structure-based models were necessary to redesign functional Ile-less proteins in most cases. We systematically replaced all 382 Ile residues from the ribosome and combined 21 redesigned subunits at a native genomic locus to produce a viable, evolutionarily stable cell. This work provides a roadmap to create the first 19-amino acid organism since early evolution.

Escherichia coli↗
PubMed2006

Small-molecule targeting of heat shock protein 90 chaperone function: rational identification of a new anticancer lead.

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and cell viability. Here we present a combined structure- and dynamics-based computational design strategy, taking the flexibility of the receptor and of a lead peptidic antagonist into account explicitly, to identify the nonpeptidic small molecule 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) as a structurally novel inhibitor of Hsp90. The compound is selected to bind the Hsp90 N-terminal domain, mimicking the chemical and conformational properties of the recently described peptidic antagonist of the survivin-Hsp90 complex, shepherdin [Plescia et al. Cancer Cell 2005, 7, 457-468]. Experimental tests show that AICAR binds the Hsp90 N-domain, destabilizes multiple Hsp90 client proteins in vivo, including survivin, and exhibits antiproliferative and proapoptotic activity in multiple tumor cell lines, while not affecting proliferation of normal human fibroblasts. We propose that AICAR represents a viable lead for further development of anticancer drugs with wide therapeutic opportunities.

Aminoimidazole Carboxamide↗
PubMed2001

An investigation of the effects of touchpad location within a notebook computer.

This study evaluated effects of the location of a notebook computer's integrated touchpad, complimenting previous work in the area of desktop mouse location effects. Most often integrated touchpads are located in the computer's wrist rest, and centered on the keyboard. This study characterized effects of this bottom center location and four alternatives (top center, top right, right side, and bottom right) upon upper extremity posture, discomfort, preference, and performance. Touchpad location was found to significantly impact each of those measures. The top center location was particularly poor, in that it elicited more ulnar deviation, more shoulder flexion, more discomfort, and perceptions of performance impedance. In general, the bottom center, bottom right, and right side locations fared better, though subjects' wrists were more extended in the bottom locations. Suggestions for notebook computer design are provided.

Adult↗
PubMed1992

Aesthetic partial-coverage dental restorations.

The literature on the subject of aesthetic partial-coverage restorations, including laminate veneers, laminate veneer bridges, composite-resin and ceramic inlays and onlays, computer-designed restorations, and etched cast restorations, has continued to expand into the 1990s. Investigations regarding fit, longevity, wear, and microleakage, as well as descriptions of clinical techniques, were well documented world-wide in 1991. The purpose of this review is to discuss some of the more important papers published during the past year.

Ceramics↗
PubMed2005

Controlling the occlusion of single restorations with CAD/CAM technology.

Computer-assisted design, computer-assisted machining (CAD/CAM) technology has received considerable clinical and research interest as a means to fabricate all-ceramic restorations. Laboratory CAD/CAM systems recreate occlusal anatomy and functional contacts using accurately articulated casts to minimize the amount of intraoral occlusal adjustment. CAD/CAM systems designed for the chairside do not use articulated casts, and yet fabricate full-contour restorations in a single appointment. Several design techniques are discussed to illustrate the 3 dimensional capability of the CAD program to plan and control occlusal contacts before milling the final restoration.

Computer Graphics↗
PubMed1997

Comprehensive life table of computer-assisted predictive mathematical relationship between age and life expectancy, survival probability or death rate in US adults.

A microcomputer program in BASIC for predicting life expectancy by age in US adults was designed. Formulas used in this study were derived from the data reported by the National Center for Health Statistics. A comprehensive life table that shows the relationship between age and death rate, survival probability or life expectancy for each year between 25 and 85 years of age was obtained in this study, using a newly designed computer program for predicting life expectancy by age and the program for survival probability previously published by the author. The comprehensive life table may be useful for clinical evaluation of patients and further helpful for biomedical investigation and epidemiological evaluation of US adults.

Adult↗
PubMed2001

Simultaneous measurements of arterial diameter and blood pressure to determine the arterial compliance, wall mechanics and stresses in vivo.

BACKGROUND: to develop a periarterial dimensional clip-probe which, associated with endovascular pressure measurement, real-time digital signal processing/data treatment systems, enables characterisation of the basic wall mechanics in given arterial sites. DESIGN: experimental study. MATERIAL: a facing pair of ultrasonic crystals was incorporated in periarterial highlight probes, made of sterilisable silicone and manufactured from computer-designed stainless steel casts. The A/D converted diameter and pressure (from an endovascular micro-tip probe) signals, triggered by the ECG, were on-line processed to provide their respective profiles during an averaged cardiac cycle, and subsequently the arterial wall physics. The technique was tested in the iliac and renal arteries in eight pigs. RESULTS: the technique was found to indicate adequately that arterial responses to distending blood pressure, as given by Petersons modulus and relative pulsatility, were identical in renals and iliacs. In contrast, the compliance, circumferential incremental elastic modulus and midwall circumferential stress were higher in iliacs than in renals, whereas arterial stiffness of the renals surpassed that of the iliacs. DISCUSSION: the technique with sterilisable probes produces in vivo pressure-diameter relationships, arterial compliance, and wall mechanics and stresses, whatever the arterial size. The porcine iliacs and renals are elastic and viscorigid arteries, respectively.

Analysis of Variance↗
PubMed1999

[Dental CT in the planning of surgical procedures. Its significance in the oro-maxillofacial region from the viewpoint of the dentist].

Dental computer assisted tomography (Dental CT) represents a valuable addition to the diagnostic spectrum for planning oral and maxillofacial surgery. High resolution CT and specially designed computer software allow representation of the jaws in different planes that are easy to match. They further allow the display of very small structures relevant to oral surgical interventions and reveal their spatial relationship in three dimensions. Thus communication between dentists and radiologists may be intensified and supported by usage of modern telecommunication systems. Dental CT is indicated, when clinical and conventional radiological techniques will not allow exact interpretation of the situation. It is modern oral implantology that primarily benefits from computer software enabling the assessment of surgical sites in the presurgical phase. Such planning was not yet possible using two dimensional radiographic techniques. The dental-implantological part expects from radiography sharply defined contours of the external bony contours and the mandibular canal, exactly defined relation between slices and planes, no distortion in the orthoradial planes, tools for reliable measurements of distances, angles and volumes, possibility to transmit pictures electronically or on hardcopy without loss of quality.

Humans↗
PubMed2005

Directed evolution strategies for improved enzymatic performance.

The engineering of enzymes with altered activity, specificity and stability, using directed evolution techniques that mimic evolution on a laboratory timescale, is now well established. However, the general acceptance of these methods as a route to new biocatalysts for organic synthesis requires further improvement of the methods for both ease-of-use and also for obtaining more significant changes in enzyme properties than is currently possible. Recent advances in library design, and methods of random mutagenesis, combined with new screening and selection tools, continue to push forward the potential of directed evolution. For example, protein engineers are now beginning to apply the vast body of knowledge and understanding of protein structure and function, to the design of focussed directed evolution libraries, with striking results compared to the previously favoured random mutagenesis and recombination of entire genes. Significant progress in computational design techniques which mimic the experimental process of library screening is also now enabling searches of much greater regions of sequence-space for those catalytic reactions that are broadly understood and, therefore, possible to model. Biocatalysis for organic synthesis frequently makes use of whole-cells, in addition to isolated enzymes, either for a single reaction or for transformations via entire metabolic pathways. As many new whole-cell biocatalysts are being developed by metabolic engineering, the potential of directed evolution to improve these initial designs is also beginning to be realised.

Journal Article↗
PubMed1995

Type-specific primer-mediated direct sequencing of consensus primer-generated PCR amplicons of human papilloma viruses: a new approach for the simultaneous detection of multiple viral type infections.

Consensus degenerate primers specific for the L1 and E1 regions were used to amplify anogenital HPV-DNA fragments. The mixture of the viral fragments was then directly sequenced with HPV-6, -11, -16, -18 and -33 type-specific computer-designed oligonucleotides as sequencing primers. The linking of a consensus primer-generated PCR amplification with type-specific primer-mediated direct sequencing and computer data bank analysis provided precise, more objective viral detection in the simultaneous presence of different HPV types. The method was successfully adapted for viral typing in clinical lesions which simultaneously contained different anogenital HPV sequences.

Anus Neoplasms↗
PubMed2006

Nonpolarizing beam splitter designed by frustrated total internal reflection inside a glass cube.

A method for the design of an all-dielectric nonpolarizing prism beam splitter utilizing the principle of frustrated total internal reflection is reported. The nonpolarizing condition for a prism beam splitter is discussed, and some single layer design examples are elaborated. The concept can be applied to a wide range of wavelengths and arbitrary transmittance values, and with the help of a computer design program examples of 400-700 nm, T(p)=T(s)=0.5+/-0.01, with incident angles of 45 degrees and 62 degrees are given. In addition, the sensitivity and application of the design are also discussed.

Journal Article↗
PubMed2001

Counselor and stimulus control enhancements of a stage-matched expert system intervention for smokers in a managed care setting.

BACKGROUND: Previous research has demonstrated the efficacy of an interactive expert system intervention for smoking cessation for a general population. The intervention provides individualized feedback that guides participants through the stages of change for cessation. Enhancing the expert system by adding proactive telephone counseling or a stimulus control computer designed to produce nicotine fading could produce preventive programs with greater population impacts. METHODS: Four interventions were compared: (a) the interactive expert system intervention; (b) the expert system intervention plus counselor calls; (c) the expert system intervention plus the stimulus control computer; and (d) an assessment only condition. A 4 (intervention) x 4 (occasions) (0,6,12, and 18 months) design was used. Smokers were contacted at home via telephone or mail. The initial subject pool was the 24,178 members of a managed care company. Screening was completed for 19,236 members (79.6%), of whom 4,653 were smokers; 85.3% of the smokers were enrolled. RESULTS: Thirty-eight percent were in the precontemplation stage, 45% in the contemplation stage, and only 17% in the preparation stage. At 18 months, the expert system resulted in 23.2% point prevalence abstinence, which was 33% greater than that of assessment only. The counselor enhancement produced increased cessation at 12 months but not at 18 months. The stimulus control computer produced no improvement, resulting in 20% worse cessation rates than the assessment only condition. CONCLUSIONS: The enhanced conditions failed to outperform the expert system alone. The study also demonstrated the ability of the interactive expert system to produce significantly greater cessation in a population of smokers than assessment alone.

Adult↗
PubMedDate not supplied

Proteomimetic libraries: design, synthesis, and evaluation of p53-MDM2 interaction inhibitors.

The p53-MDM2 interaction regulates p53-mediated cellular responses to DNA damage, and MDM2 is overexpressed in 7% of all cancers. Structure-based computational design was applied to this system to design libraries centered on a scaffold that projects side chain functionalities with distance and angular relationships equivalent to those seen in the MDM2 interacting motif of p53. A library of 173 such compounds was synthesized using solution phase parallel chemistry. The in vitro competitive ability of the compounds to block p53 peptide binding to MDM2 was determined using a fluorescence polarization competition assay. The most active compound bound with K(d) = 12 microM, and its binding was characterized by (15)N-(1)H HSQC NMR.

Binding Sites↗
PubMed1998

Cranioplasty performed with a new osteoconductive osteoinducing hydroxyapatite-derived material.

OBJECT: Cranioplasty is required to protect underlying brain, correct major aesthetic deformities, or both. The ideal material for this purpose is autogenous bone. When this is not available, alloplastic or artificial materials may be used. These materials should be malleable, strong, lightweight, inert, noncarcinogenic, nonferromagnetic, and, if possible, inexpensive. The authors reviewed their surgical experience with a new bone substitute and discuss outcomes in patients in whom it was used. METHODS: The 11 patients presented in this series had bone defects resulting from bone-involving tumor (eight cases), trauma (two cases), or aesthetic deformity due to repeated craniotomies (one case). The defects were repaired using Osprogel, a bone substitute that consists of calcium hydroxyapatite combined with synthetic, human bone-derived gelatin, glycerol, and water. Osprogel is not only a bioinert material but also an osteoconductive and osteoinducing substrate; when it is placed in contact with healthy cancellous bone, it induces osteogenesis and angiogenesis, thus permitting the regrowth of nearly normal bone. The sheet of Osprogel was modeled onto the cranial defect intraoperatively and was kept in place either by using a titanium micronet secured to surrounding bone with microscrews (first two cases) or by using a single- or double-layer titanium mesh secured with stitches. No complications due to the procedure were observed. The results, evaluated at least 6 months after surgery by using three-dimensional (3-D) reconstructed computerized tomography scans, were excellent in seven patients, good in three, and fair in one. In the patient with a fair result, the repair was unsatisfactory because there was lack of experience in using the material. In part of the area to be repaired, the Osprogel was used as filler; here it was washed out and resorbed. The cases deemed as having a good result had good bone replacement; however, the curvature was faulty. CONCLUSIONS: In the near future, this technique may be refined to achieve good or excellent results either without the use of supporting material or with the use of individual, computer-designed 3-D prostheses.

Adult↗
PubMed1984

Time is money: here's how to save money with computers.

Just three years ago, Loyola University Medical Center, with a 92 percent occupancy rate, instituted a computerized approach to housekeeping under the auspices of its building service contractor , Admiral Maintenance Service Company. To date, the Maywood , Illinois-based medical center has operated with a dramatically reduced budget and reduced its staff by 10 percent, and "is still the cleanest place in town," some patients say. I spoke with Loyola 's Director of Housekeeping, Minnie Samp 'l, and to computer designer and systems analyst Donald Campbell, of the Chicago-based contractor , to learn details.

Computers↗