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PubMedDate not supplied

Structural studies of the role of the active site metal in metalloenzymes.

This paper describes several experimental and computational methods which are currently used in the structural analysis of metal-containing macromolecules. A specific family of proteolytic enzymes which contain a zinc cation in the active site was selected to demonstrate these methods. A range of studies using one example from this family of enzymes is described which serves to clarify the role of the metal in the overall protein structure and in the local conformation of the active site in the native enzyme, the metal-deficient enzyme, and the metal-substituted enzyme and in complexes of the enzyme with various chemical analogues. The main experimental method described is X-ray crystallography, while computational methods for the examination of surface interactions and electrostatic potential effects are described briefly to complement the structural conclusions. The various experimental and computational results are then assembled in order to draw general conclusions on the structure-function relationships of metalloproteins and in particular the role of the metal in metal-containing proteolytic enzymes. The results of these studies implicate the zinc ion in the binding and catalytic activation of the substrate and stabilization of the tetrahedral reaction intermediate. It appears that in this family of enzymes a divalent metal cation is important for the required catalytic arrangement of functional groups in the active site, especially the metal ligands. However, once an appropriate metal ion is coordinated, there is practically no effect of the particular metal ion bound on either the overall three dimensional structure of the enzyme or the local detailed structure of its active site.

Amino Acid Sequence↗
PubMed2001

A computationally efficient method for obtaining standard error estimates for the promax and related solutions.

A computationally efficient algorithm for computing the asymptotic standard errors for the promax factor solution is proposed. The algorithm covers promax rotation with or without row normalization of the pre-rotated factor matrix. It also covers situations with either even- or odd-powered promax targets. With some modifications, the algorithm applies to Procrustean rotations with fixed or random independent targets. Simulation results show that the algorithm provides reasonable approximate standard errors for the promax solution with N = 200. In a real data example, the numerical results of the standard error computation using the proposed algorithm match those of an existing method based largely on the augmented information approach. The reasons why the proposed algorithm is more efficient than the augmented information approach are discussed.

Algorithms↗
PubMed1999

Pitfalls in the categorization of behaviour: a comparison of dolphin whistle classification methods.

The categorization of behaviour patterns into separate classes is crucial to the study of animal behaviour. Traditionally researchers have classified behaviour patterns through careful observation by eye. Recently this method has been increasingly replaced by computer methods. While the definition and fine scale analysis that can be achieved with computers is desirable, only a few studies have actually looked at how these methods perform in comparison with human observation. I compared the classification of bottlenose dolphin, Tursiops truncatus, whistles by human observers with the performance of three computer methods: (1) a method developed by McCowan (1995, Ethology, 100, 177-193); (2) a comparison of cross-correlation coefficients using hierarchical cluster analysis; and (3) a comparison of average difference in frequency along two whistle contours also using hierarchical cluster analysis. The whistle sample consisted of 104 randomly chosen whistles from a group of four captive bottlenose dolphins recorded both during periods when one was separate from the rest of the group and while they all swam in the same pool. The sample contained five individual-specific signature whistles and several nonsignature whistles. Five human observers, without knowledge of the recording context, were more likely than the computer methods to identify signature whistles that were used only while an animal was isolated from the rest of the group. I discuss the limitations of methods commonly used for pattern recognition in communication studies. The discrepancies between methods show how crucial it is to obtain an external validation of the behaviour classes used in studies of animal behaviour. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1989

A method for computer control of morphine ingestion by rats.

In this paper, we describe a method for controlling the administration of liquid diet and morphine to sixteen rats using a computer. Morphine ingestion treatment was performed with 6 feeding occasions per 24 hr, all experimental animals receiving similar drug doses. The amount of drug was individual and based on body weight at each feeding occasion. Control and experimental animals were kept under isocaloric conditions. Corrections of drug doses in order to compensate for changes in body weight were made every 24 hr. Sensors registered the exact time of complete drug and diet consumption and prevented overdistribution. Rats were administered 103 mg/kg b.wt. morphine during 24 hr. In another experiment rats were administered 191 mg/kg b.wt. morphine during 48 hr, and no weight loss or decrease in fluid diet intake was registered during the time of drug administration in either of the experiments. After exclusion of morphine from the fluid diet, the body weight loss was 6.1% and 8.3%, respectively, and the liquid diet intake decreased by 12.4 ml and 13.4 ml, respectively, compared with control animal intake. This demonstrates the induction of physical drug dependence. A major advantage of using computer-aided administration of morphine-admixed, fluid diet is the stepwise, small dose increments provided several times a day, resulting in higher drug dose per unit time when compared with ingestion procedures using one feeding occasion per day. The method enables rats to rapidly ingest large morphine doses under standardized conditions.

Animals↗
PubMed2005

[Design of mechanical structure dynamic characteristics and development of verification system].

OBJECTIVE: To present an effective method for structural dynamic characteristics design, required design and test means for space products' development. METHOD: Computational modal analysis method was used to evaluate natural frequencies and modes of the products in the beginning of design, and test modal analysis method was used to identify the dynamic parameters of products in the test period. RESULT: The proposed computational modal analysis system is capable of making static and dynamic analysis, as well as natural frequencies and modes analysis of the structure, and this system could be applied in mechanical structure dynamic characteristics design. The proposed test modal analysis system could acquire real time force and acceleration signals, and obtain the basic modal parameters by processing the sampled data. This system could be used to modify mechanical products' dynamic characteristics and decrease vibration amplitude. CONCLUSION: The computational and test results of two test models demonstrated that the developed computational and test modal system is effective. The method can be used for design of structural dynamic characteristics of space products.

Acceleration↗
PubMed2004

A Structural-informatics approach for tracing beta-sheets: building pseudo-C(alpha) traces for beta-strands in intermediate-resolution density maps.

We report the development of two computational methods to assist density map interpretation at intermediate resolutions: sheettracer for building pseudo-C(alpha) models of beta-sheets, and a deconvolution method for enhancing features attributed to major secondary structural elements. Sheettracer is tightly coupled with sheetminer, which was developed to locate sheet densities in intermediate-resolution density maps. The results from sheetminer are used as inputs to sheettracer, which employs a multi-step ad hoc morphological analysis of sheet densities to trace individual strands of beta-sheets. The methods were tested on simulated density maps from 12 protein crystal structures that represent a reasonably complete sampling of sheet morphology. The sheet-tracing results were quantitatively assessed in terms of sensitivity, specificity and rms deviations. Furthermore, sheettracer and the deconvolution method were rigorously tested on experimental maps of the lambda2 protein of reovirus at resolutions of 7.6A and 11.8A. Our results clearly demonstrate the capability of sheettracer in building pseudo-C(alpha) models of beta-sheets in intermediate-resolution density maps and the power of the deconvolution method in enhancing the performance of sheettracer. These computational methods, along with other related ones, should facilitate recognition and analysis of folding motifs from experimental data at intermediate resolutions.

Algorithms↗
PubMed2002

Structure activity relationship by NMR and by computer: a comparative study.

There has recently been considerable interest in using NMR spectroscopy to identify ligand binding sites of macromolecules. In particular, a modular approach has been put forward by Fesik et al. (Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Science 1996, 274, 1531-1534) in which small ligands that bind to a particular target are identified in a first round of screening and subsequently linked together to form ligands of higher affinity. Similar strategies have also been proposed for in silico drug design, where the binding sites of small chemical groups are identified, and complete ligands are subsequently assembled from different groups that have favorable interactions with the macromolecular target. In this paper, we compare experimental and computational results on a selected target (FKBP12). The binding sites of three small ligands ((2S)1-acetylprolinemethylester, 1-formylpiperidine, 1-piperidinecarboxamide) in FKBP12 were identified independently by NMR and by computational methods. The subsequent comparison of the experimental and computational data showed that the computational method identified and ranked favorably ligand positions that satisfy the experimental NOE constraints.

Binding Sites↗
PubMed1998

Evaluation of computed tomographic methods to measure vertebral rotation in adolescent idiopathic scoliosis: an intraobserver and interobserver analysis.

The purpose of this study was to compare three computed tomography (CT) measurement methods that have been described by Aaro-Dahlborn, Ho, and Krismer et al. The methods were based on clinical, intraobserver, and interobserver analysis. Twenty-five patients with adolescent idiopathic scoliosis were studied for clinical reliability of these methods. There was a significant correlation between Aaro-Dahlborn and Ho's methods (p < 0.02), and there was no correlation between Krismer's method and the other two (p > 0.05). Intraobserver analysis was performed by one observer at 20 different times, and interobserver analysis was performed by 20 orthopedic surgeons on the same CT scan. Intraobserver and interobserver analysis has shown that the method described by Ho is the most reliable one. Consequently, Ho's method is the most reliable and clinically the most useful method for measuring the vertebral rotation in adolescent idiopathic scoliosis.

Adolescent↗
PubMed1998

Fixed-point methods for computing the equilibrium composition of complex biochemical mixtures.

The fixed-point algebraic method [Storer and Cornish-Bowden (1976) Biochem. J. 159, 1-5] for computing the concentrations at equilibrium of complex biochemical mixtures fails for many binding stoichiometries, especially those that include molecular self-association. A typical example is the monomer-dimer-tetramer equilibrium. This paper reports two main results. First, the above algorithm is analysed theoretically to predict for which binding stoichiometries it succeeds and for which it will fail. Secondly, an alternative algorithm is described for self-associating biochemical systems. Illustrative examples are based on the dimeric proteinase from HIV.

Algorithms↗
PubMed2006

Integrating PET and CT information to improve diagnostic accuracy for lung nodules: A semiautomatic computer-aided method.

UNLABELLED: Our objective was to develop and evaluate 3 semiautomatic computer-aided diagnostic (CAD) schemes for distinguishing between benign and malignant pulmonary nodules by use of features extracted from CT, 18F-FDG PET, and both CT and 18F-FDG PET. METHODS: We retrospectively collected 92 consecutive cases of pulmonary nodules (<3 cm) in patients who underwent both thoracic CT and whole-body PET/CT. Forty-two of the nodules were malignant and 50 benign, as confirmed by pathologic examination and clinical follow-up. The interval between CT and PET was less than 1 mo. Four clinical parameters, including patient age, sex, smoking status, and history of previous malignancy, were used for the CAD schemes. Sixteen CT features based on size, shape, margin, and internal structure of nodules were independently rated subjectively by 2 chest radiologists. Four PET features were viewed on a PET/CT workstation. CAD schemes based on clinical parameters together with CT features, PET features, and both CT and PET features were then used to differentiate benign from malignant nodules. Finally, the output from the CAD schemes was evaluated by use of receiver-operating-characteristic analysis. RESULTS: When we used clinical parameters and CT features as input units (CAD scheme 1), the area under the receiver-operating-characteristic curve (A(z) value) of the CAD scheme was 0.83. When we used clinical parameters and PET features as input units (CAD scheme 2), the A(z) value for the computer output was 0.91. However, when we used all data as input units (CAD scheme 3), the A(z) value for the computer output was 0.95. The performance of CAD scheme 3 was better than that of CAD scheme 1 or 2. A statistically significant difference existed between the A(z) values of CAD schemes 3 and 2 (P = 0.037) and between those of CAD schemes 3 and 1 (P = 0.015). CONCLUSION: Our CAD scheme based on both PET and CT was better able to differentiate benign from malignant pulmonary nodules than were the CAD schemes based on PET alone and CT alone.

Aged↗
PubMed1991

Rapid methods and computer assisted diagnosis in medical microbiology.

Rapid diagnosis and reporting in medical microbiology is becoming more and more important. In recent years, introduction of automated instruments as well as of computer assisted diagnosis contributed to this aim. These methods, however, are very expensive. A more cost efficient and simple to perform method for rapid diagnosis is the use of specific fluorogenic substrates incorporated into culture media (solid or liquid) for identification of the most important pathogens, e.g. Escherichia coli. Investigation of Fluorocult ECD agar and Columbia agar revealed a high sensitivity (85%) and an excellent specificity (greater than 99%) of fluorescence in combination with a positive indole reaction for identification of E. coli.

Bacteria↗
PubMedDate not supplied

Evaluation of human sperm motility by means of transmembrane migration method and computer assisted semen analysis: a comparison study.

Comparing motility parameters with a trans-membrane migration method and a Hamilton-Thorn HTM-2000 computer assisted semen analyzer, we found that trans-membrane migration ratio (TMMR) correlated best with critical motility which indicated the fraction of fastest and straightest sperm in a semen sample. We also found that TMMR correlated better with progressive velocity than with track speed. It is concluded that nonprogressive sperm were not included in the estimation of TMMR and the trans-membrane migration method is most suitable for studying drug effect on straight and rapid sperm motility.

Computers↗
PubMed2004

Virtual screening methods that complement HTS.

In this review, we discuss a number of computational methods that have been developed or adapted for molecule classification and virtual screening (VS) of compound databases. In particular, we focus on approaches that are complementary to high-throughput screening (HTS). The discussion is limited to VS methods that operate at the small molecular level, which is often called ligand-based VS (LBVS), and does not take into account docking algorithms or other structure-based screening tools. We describe areas that greatly benefit from combining virtual and biological screening and discuss computational methods that are most suitable to contribute to the integration of screening technologies. Relevant approaches range from established methods such as clustering or similarity searching to techniques that have only recently been introduced for LBVS applications such as statistical methods or support vector machines. Finally, we discuss a number of representative applications at the interface between VS and HTS.

Animals↗
PubMed1995

Improved method for computation of potentials in a realistic head shape model.

The Lead Field Analysis (LFA) algorithm, a new computational technique for the calculation of potentials on the surface of a realistic head shaped volume conductor model based on the Boundary Element Method and the Reciprocity Theorem, is presented. The new algorithm, in comparison to the Standard Boundary Element Method, offers improved computational efficiency and lower storage requirements. It also yields more accurate surface potential results in the face of varying dipole source locations for a head shape Boundary Element model with a given number of nodes. Additionally, the algorithm results in quasi-analytic expressions of the derivatives of the surface potential with respect to the location of the sources, allowing the use of optimization techniques with better convergence properties. A set of simulations demonstrating the increased robustness of the LFA Algorithm in the face of varying dipole source parameters is also described.

Algorithms↗