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PubMed1993

Treatment of extensive cranial bone defects using computer-designed hydroxyapatite ceramics and periosteal flaps.

We performed cranioplasty using hydroxyapatite ceramics and periosteal flaps in three patients with extensive cranial bone defects. These defects were left after post-brain surgery infection forced the removal of cranial bone. Hydroxyapatite ceramics made by using computer-aided design from three-dimensional computed tomographic image data were implanted in these patients. The defects were relatively large (the largest was 16.5 x 7.5 cm) and had a high degree of curvature. Three pieces were required in one patient, although one piece was sufficient in the other two patients. The surgical technique consisted of removal of the epidural granulation tissue, exposure of the cranial bone defect site, and shaping of the hydroxyapatite ceramics to fit the defect entirely, followed by the implantation of the hydroxyapatite ceramics. In anticipation of induction of the bone to hydroxyapatite, we covered the hydroxyapatite ceramics with periosteal flaps of cranial bones; however, based on only these three patients, our knowledge of the ossification-promoting effect is incomplete. More clinical cases should be investigated to evaluate further the clinical efficacy of this method for treatment. As we have reported here, the treatment of cranial bone defects by using computer-designed hydroxyapatite ceramics and a periosteal flap is safe and highly effective.

Adult↗
PubMed2005

A computer-designed macrocyclic zinc receptor.

A macrocycle containing a pair of bipyridine moieties with a linker designed using the computer program CAVEAT exhibits unique selectivity in the binding of zinc ion relative to other metals.

Journal Article↗
PubMed2001

"Bite-and-Switch" approach using computationally designed molecularly imprinted polymers for sensing of creatinine.

A method for the selective detection of creatinine is reported, which is based on the reaction between polymerised hemithioacetal, formed by allyl mercaptan, o-phthalic aldehyde, and primary amine leading to the formation of fluorescent isoindole complex. This method has been demonstrated previously for the detection of creatine using creatine-imprinted molecularly imprinted polymers (MIPs) Since MIPs created using traditional methods were unable to differentiate between creatine and creatinine, a new approach to the rational design of a molecularly imprinted polymer (MIP) selective for creatinine was developed using computer simulation. A virtual library of functional monomers was assigned and screened against the target molecule, creatinine, using molecular modelling software. The monomers giving the highest binding score were further tested using simulated annealing in order to mimic the complexation of the functional monomers with template in the monomer mixture. The result of this simulation gave an optimised MIP composition. The computationally designed polymer demonstrated superior selectivity in comparison to the polymer prepared using traditional approach, a detection limit of 25 microM and good stability. The "Bite-and-Switch" approach combined with molecular imprinting can be used for the design of assays and sensors, selective for amino containing substances.

Biosensing Techniques↗
PubMed2002

Computational design and prediction of interesting not-yet-synthesized structures of inorganic materials by using building unit concepts.

The computational design of new and interesting inorganic materials is still an ongoing challenge. The motivation of these efforts is to aid the often difficult task of crystal structure determination, to rationalize different but related structure types, or to help limit the domain of structures that are possible in a given system. Over the past decade, simulation methods have continuously evolved towards the prediction of new structures using minimal input information in terms of symmetry, cell parameters, or chemical composition. So far, this task of identifying candidate structures through an analysis of the energy landscape of chemical systems has been particularly successful for predominantly ionic systems with relatively small numbers of atoms or ions in the simulation cell. After an introductory section, the second section of this work presents the historical developments of such simulation methods in this area. The following sections of the work are dedicated to the introduction of the building unit concept in simulation methods: we present simulation approaches to structure prediction employing both primary (aggregate of atoms) and secondary (aggregate of coordination polyhedra) building units. While structure prediction with primary units is a straightforward extension of established approaches, the AASBU method (automated asssembly of secondary building units) focusses on the topology of network-based structures. This method explores the possible ways to assemble predefined inorganic building units in three-dimensional space, opening the way to the manipulation of very large building units (up to 84 atoms in this work). As illustrative examples we present the prediction of candidate structures for Li(4)CO(4), the identification of topological relationships within a family of metalphosphates, ULM-n and MIL-n, and finally the generation of new topologies by using predefined large building units such as a sodalite or a double-four-ring cage, for the prediction of new and interesting zeolite-type structures.

Journal Article↗
PubMed1992

Three dimensional imaging and computer-designed prostheses in the evaluation and management of orbitocranial deformities.

Three dimensional images reconstructed from two dimensional CT scans allow improved analysis of complex orbitocranial bony deformities. This evaluation may be useful in patients with defects resulting from trauma, tumor, congenital abnormalities, or developmental disorders. Diagnosis, surgical management, and long-term follow-up evaluation may be aided by improved understanding of bony contour and volume analysis. Computer designed prostheses can be fabricated to precisely match bony defects and may be used as an alloplastic implant or as a model to aid intraoperative contouring of an autogenous bone graft. The limitations of three dimensional imaging include artifacts in the reconstructed images, increased radiation exposure, and increased cost. The technology is still evolving and the indications and benefits remain undefined at the present time.

Adolescent↗
PubMed1993

An attempt to substitute the cell binding domain of human fibronectin in lambda phage J protein: computer design and expression.

We superimposed hydropathic indexes of the human fibronectin cell binding domain (CBD) on the lambda phage J protein by computer, and substituted 22 amino acids from the fibronectin CBD for a part of the lambda phage J protein. The fibronectin cell binding domain -Arg-Gly-Asp-Ser- (-RGDS-) localizes at the junction of hydrophobicity and hydrophilicity. We selected a similar hydrophobic-to-hydrophilic junction in the J protein region for substitution. This junction corresponds to 150 bp of the PstI fragment of J protein cDNA. We synthesized 150 bp of the relevant PstI fragment that includes the cell binding domain region. The region was then constructed by serial cloning as an expression vector, pJCBD. The vector pJCBD expressed the fused protein named JCBD (M(r) 32 kDa) in E coli XL1-BLUE. The expressed JCBD protein was identified by Western blot analysis in the extract of the pJCBD carrying bacterial lysate using both rabbit anti-lambda phage antiserum and anti-CBD of fibronectin antibody. The JCBD protein appeared to recognize retinoblast cell membrane RGDS-directed receptors, detected by enzyme-linked immuno-sorbent assay and also by binding competition assay with synthetic pentapeptides, Gly-Arg-Gly-Asp-Ser (GRGDS) and Gly-Arg-Gly-Glu-Ser (GRGES). The former competitor inhibited completely fibronectin CBD-dependent binding activity of JCBD, the latter had no inhibitory activity. These results suggest that certain functional proteins engineered by computer design between human fibronectin cell binding domain and lambda phage J protein can be produced.

Amino Acid Sequence↗
PubMed1996

Computational design of a substrate specificity mutant of a protein.

The wild-type trp repressor of E. coli bound 5-methoxytryptophan, a Trp analogue, less tightly than Trp. A mutant repressor (Val58-->Ala) that should bind 5-methoxytryptophan preferentially to Trp was computationally designed by free-energy calculations accompanied by free-energy decomposition. The designed mutant was demonstrated by experiments to bind 5-methoxytryptophan more tightly than Trp, consistent with the computational prediction. This success indicates the usefulness of free energy decomposition in protein design.

Bacterial Proteins↗
PubMed2001

Reducing constraints on quantum computer design by encoded selective recoupling.

The requirement of performing both single-qubit and two-qubit operations in the implementation of universal quantum logic often leads to very demanding constraints on quantum computer design. We show here how to eliminate the need for single-qubit operations in a large subset of quantum computer proposals: those governed by isotropic and XXZ, XY-type anisotropic exchange interactions. Our method employs an encoding of one logical qubit into two physical qubits, while logic operations are performed using an analogue of the NMR selective recoupling method.

Journal Article↗
PubMed2004

Computational design of a biologically active enzyme.

Rational design of enzymes is a stringent test of our understanding of protein chemistry and has numerous potential applications. Here, we present and experimentally validate the computational design of enzyme activity in proteins of known structure. We have predicted mutations that introduce triose phosphate isomerase activity into ribose-binding protein, a receptor that normally lacks enzyme activity. The resulting designs contain 18 to 22 mutations, exhibit 10(5)- to 10(6)-fold rate enhancements over the uncatalyzed reaction, and are biologically active, in that they support the growth of Escherichia coli under gluconeogenic conditions. The inherent generality of the design method suggests that many enzymes can be designed by this approach.

Algorithms↗
PubMed2002

Novel inorganic frameworks constructed from double-four-ring (D4R) units: computational design, structures, and lattice energies of silicate, aluminophosphate, and gallophosphate candidates.

The design of new and interesting inorganic frameworks is an ongoing challenge in materials sciences. New structures containing double-four-ring (D4R) units have recently received particular attention. The present work focuses on the computational design of new three-dimensional frameworks made of D4R units exclusively. In a first step, our simulations explore the possible ways to assemble predefined D4R units in 3D space using a sophisticated cascade of simulated annealing/minimizations steps (autoassembly of secondary building units method). While the existing zeotype topologies were successfully generated, new topologies were predicted including very open frameworks containing new types of cages. In a second step, lattice energy minimizations were performed to estimate the viability of these hypothetical frameworks as silicate, aluminophosphaste, and gallophosphate candidates. When comparing the hypothetical structures to existing compounds, our results raise the challenging question of the appropriate chemical composition that should be aimed at for a given framework topology of interest.

Journal Article↗
PubMed1988

Computer-designed prostheses for orbitocranial reconstruction.

Three-dimensional imaging is an adjunct to preoperative evaluation and surgical management in some patients with complex anatomic defects of various etiologies. Deformities defined by conventional computerized tomography can be viewed as accurate three-dimensional images calculated from the original scan. The images are viewed on a high-resolution video monitor and can be photographed for a permanent record. A computer-controlled milling device can use these data to fabricate prostheses. The prostheses aid reconstructive surgery through use as an alloplastic implant, as a template to fashion autogenous bone grafts, or as a model for tissue removal. We have utilized three-dimensional imaging in combination with computer-assisted prosthesis manufacture in six patients with complex orbitocranial deformities. Four patients have undergone reconstructive surgery with satisfactory results and no complications thus far. The use of computer-designed prostheses adds a new aspect to orbitocranial reconstructive surgery that facilitates increased accuracy in the correction of anatomic defects.

Adolescent↗
PubMed2006

[Computer aided design and computer aided manufacture of sacrificial pattern of removable partial denture framework].

OBJECTIVE: To introduce a method applied in computer aided design and computer aided manufacture (CAD-CAM) of removable partial denture framework for rehabilitating edentulous arch of Kennedy Class II and found a basis for this project. METHODS: Point cloud data of dental stone model was obtained by laser scanning. The following processes were made: drawing framework outline on the reconstructed triangle mesh model, picking up and processing its inner side data as the data of tissue surface, shelling it for 3-D model of framework, and transferring the data to rapid prototyping equipment for manufacture. RESULTS: 3-D model of the removable partial denture framework was preliminarily accomplished. The resin framework used as a sacrificial pattern was manufactured with the rapid prototyping equipment. The fit between resin framework and plaster model was good. CONCLUSIONS: This method, as an integrated procedure including data acquisition, 3-D computer modeling and fabrication by rapid prototyping, is feasible to implement CAD-CAM of removable partial denture framework.

Computer-Aided Design↗
PubMed2005

Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes.

Allosteric RNAs operate as molecular switches that alter folding and function in response to ligand binding. A common type of natural allosteric RNAs is the riboswitch; designer RNAs with similar properties can be created by RNA engineering. We describe a computational approach for designing allosteric ribozymes triggered by binding oligonucleotides. Four universal types of RNA switches possessing AND, OR, YES and NOT Boolean logic functions were created in modular form, which allows ligand specificity to be changed without altering the catalytic core of the ribozyme. All computationally designed allosteric ribozymes were synthesized and experimentally tested in vitro. Engineered ribozymes exhibit >1,000-fold activation, demonstrate precise ligand specificity and function in molecular circuits in which the self-cleavage product of one RNA triggers the action of a second. This engineering approach provides a rapid and inexpensive way to create allosteric RNAs for constructing complex molecular circuits, nucleic acid detection systems and gene control elements.

Allosteric Site↗
PubMed2006

Ultrafast folding of a computationally designed Trp-cage mutant: Trp2-cage.

Miniproteins provide useful model systems for understanding the principles of protein folding and design. These proteins also serve as useful test cases for theories of protein folding, and their small size and ultrafast folding kinetics put them in a regime of size and time scales that is now becoming accessible to molecular dynamics simulations. Previous estimates have suggested the "speed limit" for folding is on the order of 1 mus. Here a computationally designed mutant of the 20-residue Trp-cage miniprotein, Trp2-cage, is presented. The Trp2-cage has greater stability than the parent and folds on the ultrafast time scale of 1 mICROs at room temperature, as determined from infrared temperature-jump experiments.

Computer Simulation↗
PubMed1998

The design, computer modeling, solution structure, and biological evaluation of synthetic analogs of bryostatin 1.

The bryostatins are a unique family of emerging cancer chemotherapeutic candidates isolated from marine bryozoa. Although the biochemical basis for their therapeutic activity is not known, these macrolactones exhibit high affinities for protein kinase C (PKC) isozymes, compete for the phorbol ester binding site on PKC, and stimulate kinase activity in vitro and in vivo. Unlike the phorbol esters, they are not first-stage tumor promoters. The design, computer modeling, NMR solution structure, PKC binding, and functional assays of a unique class of synthetic bryostatin analogs are described. These analogs (7b, 7c, and 8) retain the putative recognition domain of the bryostatins but are simplified through deletions and modifications in the C4-C14 spacer domain. Computer modeling of an analog prototype (7a) indicates that it exists preferentially in two distinct conformational classes, one in close agreement with the crystal structure of bryostatin 1. The solution structure of synthetic analog 7c was determined by NMR spectroscopy and found to be very similar to the previously reported structures of bryostatins 1 and 10. Analogs 7b, 7c, and 8 bound strongly to PKC isozymes with Ki = 297, 3.4, and 8.3 nM, respectively. Control 7d, like the corresponding bryostatin derivative, exhibited weak PKC affinity, as did the derivative, 9, lacking the spacer domain. Like bryostatin, acetal 7c exhibited significant levels of in vitro growth inhibitory activity (1.8-170 ng/ml) against several human cancer cell lines, providing an important step toward the development of simplified, synthetically accessible analogs of the bryostatins.

Animals↗
PubMed2001

Computational design of direct-bandgap semiconductors that lattice-match silicon.

Crystalline silicon is an indirect-bandgap semiconductor, making it an inefficient emitter of light. The successful integration of silicon-based electronics with optical components will therefore require optically active (for example, direct-bandgap) materials that can be grown on silicon with high-quality interfaces. For well ordered materials, this effectively translates into the requirement that such materials lattice-match silicon: lattice mismatch generally causes cracks and poor interface properties once the mismatched overlayer exceeds a very thin critical thickness. But no direct-bandgap semiconductor has yet been produced that can lattice-match silicon, and previously suggested structures pose formidable challenges for synthesis. Much recent work has therefore focused on introducing compliant transition layers between the mismatched components. Here we propose a more direct solution to integrating silicon electronics with optical components. We have computationally designed two hypothetical direct-bandgap semiconductor alloys, the synthesis of which should be possible through the deposition of specific group-IV precursor molecules and which lattice-match silicon to 0.5-1% along lattice planes with low Miller indices. The calculated bandgaps (and hence the frequency of emitted light) lie in the window of minimal absorption in current optical fibres.

Journal Article↗