Abstract: A method of displaying gene data assists in discovering expression patterns specific to gene functions and inferring the function of a gene of which the function is unknown. A threshold value representing the degree of similarity of expression patterns is established in advance, and genes having the same function and genes with similar expression patterns to them are extracted and displayed. Cluster analysis is performed on the extracted genes by re-selecting the experiment patterns for clustering. Calculations are performed to see how many functions the genes belonging to a subtree have, and the proportion of each function in the subtree is determined. If a proportion exceeds a predetermined threshold value, they are regarded as a cluster (collection of genes with similar functions) and extracted.

Abstract: A WW domain crystal structure of Pin1 is provided. In addition, methods of using the crystal structure and atomic coordinates for the development of WW domain binding agents is also provided. Also provided are computer programs on computer readable medium for use in developing WW domain binding agents.

Abstract: A system and method for reconstructing pathways in large genetic networks from genetic perturbations comprises an analysis method and system that applies a recursive algorithm for determining the path between every gene pair in an arbitrarily large genetic network from large-scale gene perturbation data and reconstructs all direct and indirect regulatory gene interactions in the network. Graph theory mathematics is applied to genetic network reconstruction in the following manner: Genetic perturbation data is used to identify all genes accessible from a perturbed gene to generate an accessibility list for the gene. Graph theory mathematics is applied to the accessibility list and its graph to determine a condensation of the graph as defined by the condensation's accessibility list. Graph theory mathematics is applied to the accessibility list, such as through a recursive algorithm performed on a desktop computer, to obtain an adjacency list for the gene that characterizes a genetic network.

Abstract: The objective of the present invention is the efficient analyzation of the structure of an array. By performing the prev(S) calculation for a character string S, if in S, a like variable is present upstream of a second variable, the second variable is changed to a numerical value that indicates the distance to the upstream like variable. But if in S, a like variable is not present upstream of a variable, that variable is changed to “0” to obtain a character string S1. Further, by performing the compl(S) calculation for S, if in the character string S a complementary variable is present upstream of a second variable, the second variable is changed to a numerical value that indicates the distance to the complementary variable. But if in S, a complementary variable is not present upstream of a variable, that variable is changed to “0” to obtain a character string S2.

Abstract: The invention relates to methods of identifying and characterizing properties of polymers to provide information about the polymer such as the charge of the polymer, the number and types or characteristics of units of the polymer and the sequence of the polymers. The invention also relates to methods of sequencing polymers such as nucleic acids, polypeptides and polysaccharides and methods for identifying a polysaccharide-protein interaction.

Abstract: The invention relates to methods of identifying and characterizing properties of polymers to provide information about the polymer such as the charge of the polymer, the number and types or characteristics of units of the polymer and the sequence of the polymers. The invention also relates to methods of sequencing polymers such as nucleic acids, polypeptides and polysaccharides and methods for identifying a polysaccharide-protein interaction.

Abstract: I describe several techniques for characterizing molecules based on the shapes of their fields. The minimal distance between two molecular fields is used as a shape-based metric, independent of the underlying chemical structure, and a high-dimensional shape space description of the molecules is generated. I then show how these attributes can be used in creating, characterizing, and searching databases of molecules based on field similarity. In particular, they allow searches of a database in sublinear time. Next, I extend the utility of this approach by describing a way to automatically break molecules into a series of fragments by using an ellipsoidal Gaussian decomposition. Not only can these fragments then be analyzed by the shape metric technique described above, but the parameters of the decomposition themselves can also be used to further organize and search databases. The most immediate application of these techniques is to pharmaceutical drug discovery and design.

Abstract: The disclosure relates to a method of estimating the polar component of the solvation energy for a molecule embedded in different media. In one embodiment, the molecule is partially embedded in a membrane. For an atom of the molecule, the polar component of the atom's solvation energy is represented as a combination of at least a self-energy term and a screening-effect term. The self-energy term represents the contribution to the atom's polar component made by the membrane and the molecule's other atoms located inside the membrane. The screening-effect term represents the typically negative contribution to the atom's polar component made by the molecule's other atoms located outside the membrane. An analytical function is used to calculate the self-energy term.

Abstract: The present invention is directed to a method for determining the molecular weight and diffusivity of a sample solute by providing a plus shaped microchannel network on a microfluidic chip, having at least four microchannels intersecting at a cross point; flowing a sample stream comprising a sample solute of unknown diffusivity and a blank stream from separate microchannels through the cross point and out to separate microchannels; creating a sample curve measuring the concentration of the sample solute that diffuses from the sample stream to the blank stream at the cross point while altering the flowrate of one of the blank stream or the sample stream; and determining a diffusion coefficient of the sample solute by extrapolating data from similar curves of at least two solutes having known molecular weights and/or diffusion coefficients created under similar conditions as those generated by the sample solute.

Abstract: A method of protein engineering is provided wherein a searchable computer database is created comprising entries in the form of descriptions of a location and orientation in 3D space of side chains of the constituent amino acid residues of a framework protein. A query is created which corresponds to a description of a location and orientation in 3D space of respective side chains of amino acid residues of a sample protein. The location and orientation in 3D space of constituent side-chains is preferably described as a C?–C? vector. The query is used to search the database and thereby identify a hit which corresponds to a framework protein having structural similarity with said sample protein. Framework protein “hits” so identified may be suitable candidates for further modification. A particular advantage of the present invention is that a modified framework protein may display one or more desired characteristics, such as a function similar to or inhibitory of the sample protein.

Abstract: An optical scanning system adapted to physically adjust scanner settings in response to control feature readings is disclosed. The scanner and methodology finds particular use in reading of biopolymer arrays. The system may operate in any of a number of ways such that optimal data from scans is obtained. It may also be possible to use the system as a tool to aid in manufacture of arrays by providing feedback to a manufacturer regarding the signal produce for a given batch of samples tested.

Abstract: Crystalline IGF-1 is provided along with a method for production thereof. Crystallizing IGF-1 comprises the steps of mixing an aqueous solution comprising IGF-1 with a reservoir solution comprising a precipitant to form a mixture; and crystallizing the mixture, optionally also recrystallizing and isolating the crystalline IGF-1. In addition, a method for identifying IGF-1 indirect agonists is provided using a detergent as a standard for the level of inhibition of binding of IGFBP-1 or IGFBP-3 to IGF-1 and/or using the coordinates of the binding pockets of IGF-1 to which a candidate indirect agonist binds for structure-based drug design.

Abstract: Structure factor bias in an electron density map for an unknown crystallographic structure is minimized by using information in a first electron density map to elicit expected structure factor information. Observed structure factor amplitudes are combined with a starting set of crystallographic phases to form a first set of structure factors. A first electron density map is then derived and features of the first electron density map are identified to obtain expected distributions of electron density. Crystallographic phase probability distributions are established for possible crystallographic phases of reflection k, and the process is repeated as k is indexed through all of the plurality of reflections. An updated electron density map is derived from the crystallographic phase probability distributions for each one of the reflections. The entire process is then iterated to obtain a final set of crystallographic phases with minimum bias from known electron density maps.

Abstract: The invention provides high resolution X-ray crystal structures of the 30S ribosome, obtained from Thermus thermophilus 30S subunit, having a tetragonal space group P41212 to which are bound an antibiotic selected from the group paromomycin, streptomycin, spectinomycin, tetracycline, pactamycin and hygromycin B. An advantageous feature of the structure is that it diffracts at about 3 ? resolution. The invention also provides a crystal of 30S having the three dimensional atomic coordinates of the 30S ribosome, the coordinates being provided in any one of tables 1 to 4. The data may be used for the rational design and modelling of inhibitors for the 30S ribosome, which have potential use as antibiotics.

Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a central signaling enzyme in a cell nucleus. PARP-1 is a target for the development of radio and chemo sensitizing agents in cancer treatment as well as providing protection from stroke. An SH3 domain and an SH3 ligand domain have now been discovered on the PARP-1 protein. These domains are involved in PARP-1 activation. This discovery makes possible the use of bioinformatics tools for the design of new drugs and strategies for drug target selection, specifically targeting the PARP-1 enzyme.

Abstract: The present invention provides a method for identifying inhibitors of protein kinases. Methods are also provided for inhibiting protein kinase activity. Specific non-peptide protein tyrosine kinase inhibitor are provided. The protein kinases produced using the method of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, or immune system activity.

Abstract: Methods and apparatuses are disclosed that model the lineshapes of mass spectrometry data. Ions can be modeled with an initial distribution that models molecules as having multiple positions and/or energies prior to traveling in the mass spectrometer. These initial distributions can be pushed forward by time of flight functions. Fitting can be performed between the modeled lineshapes and empirical data. Filtering can greatly reduce dimensions of the empirical data, remove noise, compress the data, recover lost and/or damaged data.

Abstract: An apparatus for identifying a protein, polypeptide or peptide by means of mass spectrometry and especially by tandem mass spectrometry is disclosed. The apparatus preferably functions to model the fragmentation of a peptide or protein in a tandem mass spectrometer to facilitate comparison with an experimentally determined spectrum. A fragmentation model is used which takes account of all possible fragmentation pathways which a particular sequence of amino acids may undergo. A peptide or protein may be identified by comparing an experimentally determined mass spectrum with spectra predicted using such a fragmentation model from a library of known peptides or proteins.

Abstract: The present invention relates to protein separation systems and methods capable of resolving and characterizing large numbers of cellular proteins. In particular, the present invention provides a novel mass mapping system and methods for the differential display of proteins. The present invention further provides novel methods for displaying differential protein expression between two samples. In particular, the present invention provides novel method of mapping differential expression of proteins in non-cancerous, pre-cancerous, and cancerous cells.

Abstract: The present invention relates to crystallized molecules and molecular complexes which comprise the active site binding pocket or the FKBP12/FK506 binding pocket of calcineurin or close structural homologues to either binding pocket. This invention also relates to a data storage material encoded with the corresponding structure coordinates of those crystallized molecules or molecular complexes. Such data storage material is capable of displaying such molecules and molecular complexes as a graphical three-dimensional representation on a computer screen. In addition, this invention relates to methods of using the structure coordinates of those molecules or molecular complexes to solve the structure of homologous proteins. This invention also relates to methods of using the structure coordinates to screen and design compounds that bind to calcineurin or homologues thereof.

Abstract: A high-throughput molecular docking facility is presented for screening combinatorial libraries to identify binding ligands and ultimately pharmaceutical compounds. The facility employs a pre-docking conformational search to generate multiple solution conformations of a ligand. The molecular docking facility includes: generating a binding site image of the protein, the binding site image having multiple hot spots; matching hot spots of the binding site image to atoms in at least one solution conformation of the multiple solution conformations of the ligand to obtain at least one ligand position relative to the protein in a ligand-protein complex formation; and optimizing the at least one ligand position while allowing translation, orientation and rotatable bonds of the ligand to vary, and while holding the protein fixed.

Abstract: A simulation device calculates an equilibrium arrangement of a set of particles by using a potential function or a force function, which describes an interaction of a particle system, and simulates the particle system by using an obtained equilibrium arrangement as an initial arrangement.

Abstract: The invention provides for in silico analysis of a virtual combinatorial library. Mapping coordinates for a training subset of products in the combinatorial library, and features of their building blocks, are obtained. A supervised machine learning approach is used to infer a mapping function ƒ that transforms the building block features for each product in the training subset of products to the corresponding mapping coordinates for each product in the training subset of products. The mapping function ƒ is then encoded in a computer readable medium. The mapping function ƒ can be retrieved and used to generate mapping coordinates for any product in the combinatorial library from the building block features associated with the product.

Abstract: Disclosed herein are methods of selecting probes to target nucleic acid sequences, methods of making oligonucleotide arrays comprising such probes, and methods of using such arrays. Also, described herein are oligonucleotide arrays comprising probes selected by a method of the invention.

Abstract: A technique is described for quantitating biological indicators, such as viral load, using interferometric interactions such as quantum resonance interferometry. A diffusion curve for the biological indicator of interest is generated from at least two measurements from a patient sample. In some embodiments, the patient samples are in the form of a microarray output pattern to which the patient sample has been applied. After the diffusion curve has been generated, subsequent patient samples are mapped to the diffusion curve to provide a quantitative measure of the biological indicator of interest.

Abstract: A method for determining the molecular diffusivity of a solute in a microchannel where a solute is introduced into a first end of a microchannel and a first concentration profile is measured at first and second locations along the microchannel. A theoretical concentration profile can be calculated at the second location based on the measured first concentration profile at the first location. The molecular diffusivity can be found by minimizing the error when comparing the theoretical concentration profile to the measured second concentration profile. Further, this technique allows for average velocity to be measured simultaneously with molecular diffusivity.

Abstract: A system for characterizing geometric structures formed on a sample on a real time basis is disclosed. A multi-parameter measurement module generates output signals as a function of either wavelength or angle of incidence. The output signals are supplied to a parallel processor. The processor creates an initial theoretical model and then calculates the theoretical optical response of that sample. The calculated optical response is compared to measured values. Based on the comparison, the model configuration is modified to be closer to the actual measured structure. The processor recalculates the optical response of the modified model and compares the result to the measured data. This process is repeated in an iterative manner until a best fit is achieved. The steps of calculating the optical response of the model is distributed to the processors as a function of wavelength or angle of incidence so these calculations can be performed in parallel.

Abstract: A method that analyzes mass spectra using a digital computer is disclosed. The method includes entering into a digital computer a data set obtained from mass spectra from a plurality of samples. Each sample is, or is to be assigned to a class within a class set having two or more classes and each class is characterized by a different biological status. A classification model is then formed. The classification model discriminates between the classes in the class set.

Abstract: The invention relates to reference libraries of composite spectra that consolidate, into a single searchable data set, multiple independent spectra taken of a chemical compound under multiple conditions, generally on a single instrument. The reference libraries may be used, for example, to increase the analytical power of mass spectrometers such as API-CID mass spectrometers. The multiple independent spectra are converted into a composite spectrum by performing a number of steps. First, units on the x-axis of at least one, and generally all but one, of the independent spectra are renumbered so that the numerical range of the x-axes of the spectra do not perfectly overlap. Second, the x-axes of the independent spectra are aligned on a composite x-axis. Methods and programs for making and using the reference libraries and devices containing the reference libraries are also disclosed.

Abstract: Identification of the human insulin receptor binding site sequence of certain spatial molecular structures conforming to such binding site and of certain insulinomimetic sequences including the binding site sequence are disclosed.

Abstract: The present invention provides a method and a system for searching for relationships between base sequences in order to efficiently analyze the relationship between a sample base sequence and known base sequences. In the system, a theoretical value calculating portion calculates theoretical restriction fragment length values based on restriction enzyme data. The comparing portion produces analysis result data by comparing theoretical restriction fragment patterns with measured restriction fragment patterns, calculating the degree of similarity of the sample base sequence to known base sequences.

Abstract: A segmentation method of a frame of image information including a plurality of spaced DNA spot images corresponding to a plurality of DNA spots. The image information includes image intensity level information corresponding to said DNA spots. The frame is stored in a memory device and a set of image information within said frame including a selected set of the DNA spot images is selected. A grid including a plurality of spaced grid points corresponding to said selected DNA spot images is generated, such that each grid point includes position information indicating the position of the grid point within said frame.

Abstract: An unliganded form of Staphylococcus aureus NAD synthetase (S. aureus NadE) has been crystallized, and the three-dimensional x-ray crystal structure has been solved to 2.3 ? resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of S. aureus NadE activity.

Abstract: There is provided a method for obtaining at least one calibration filter for a Mass Spectrometry (MS) instrument system. Measured isotope peak cluster data in a mass spectral range is obtained for a given calibration standard. Relative isotope abundances and actual mass locations of isotopes corresponding thereto are calculated for the given calibration standard. Mass spectral target peak shape functions centered within respective mass spectral ranges are specified. Convolution operations are performed between the calculated relative isotope abundances and the mass spectral target peak shape functions to form calculated isotope peak cluster data. A deconvolution operation is performed between the measured isotope peak cluster data and the calculated isotope peak cluster data after the convolution operations to obtain the at least one calibration filter.

Abstract: The present invention provides a method and apparatus to significantly accelerate the searching process based on the Monte Carlo principle and the lattice model. Specifically, the energy status of a lattice-based protein conformation is evaluated by modeling the folding process through a pipelined digital circuit using a number of state machines. The pipelined digital circuit reduces the time required for the determination of the energy status of a particular conformation and, therefore, significantly accelerates the searching speed for the lowest energy status. The present invention also permits real-time tuning of problem parameters by the experimenter.

Abstract: Apparatus and a method are described for investigating polymorphs of a material, isomers of a material which allow different isomeric forms to be resolved, different hydrates/solvates and/or different salts of a material. The apparatus comprises an assembly (2) of reactor devices (6) arranged within a reactor body (8) which incorporates a heating/cooling block (10) and a stirrer block (12). A vessel support block (14) supports respective sample vessels (15) below each reactor device (6) for recieving material from the reactor devices. The apparatus includes a control unit (4) which includes a computer (16) which controls a robot for delivering materials to the reactor devices; a heating/cooling unit (18); a stirrer control unit (20); and a pressure unit (22) which controls the passage of material from the reactor devices (6) to the sample vessels (15).

Abstract: The present invention relates to methods and agonist/antagonist compounds for modulating nuclear receptor coactivator binding. The invention includes a method for identifying residues comprising a coactivator binding site for a nuclear receptor of interest. Also included is a method of identifying agonists and/or antagonists that bind to a coactivator binding site of a nuclear receptor of interest. Agonists and antagonists of coactivator binding to nuclear receptors also are provided. The invention is exemplified by identification and manipulation of the coactivator binding site of the thyroid receptor (TR), and compounds that bind to this sites. The methods can be applied to other nuclear receptors including RAR, RXR, PPAR, VDR, ER, GR, PR, MR, and AR.

Abstract: A fully automated, user-independent method is described for computer-mediated interpretation of data derived by mass spectrometry of an experimental peptide to identify and characterize a corresponding peptide sequence in a peptide database. The method identifies the corresponding sequence if it is present in the database, without the need for a skilled observer to choose from amongst a list of possible matches. By using an automated back-read process, the present method can uniquely identify a corresponding peptide sequence in a database based on a single matching peptide sequence. The method also permits mapping of mass spectral data to sequences in peptide or nucleotide databases for unambiguous identification of exons; determining a correct reading frame; identifying artefacts and errors in sequences; identifying mutations and polymorphisms; identifying post-translational modifications; and identifying exon-intron boundaries.

Abstract: A technique for determining events of interest within an output pattern generated from a detected image of an array of detectors where the output pattern comprises signals associated with noise, and signals associated with the events of interest which have intensities both greater and less than intensities of signals associated with noise. Quantum resonance interferometry is utilized to amplify signals associated with the events of interest having an intensity lower than the intensity of signals associated with noise, to an intensity greater than the intensity of the signals associated with noise to generate a modified output pattern. Once the desired signals are amplified, the technique determines which signals within the modified output pattern correlate with events of interest thus permitting a determination to be made whether a certain event of interest has occurred.

Abstract: In particular, this invention provides novel methods of populating data structures for use in evolutionary modeling. In particular, this invention provides methods of populating a data structure with a plurality of character strings. The methods involve encoding two or more a biological molecules into character strings to provide a collection of two or more different initial character strings; selecting at least two substrings from the pool of character strings; concatenating the substrings to form one or more product strings about the same length as one or more of the initial character strings; adding the product strings to a collection of strings; and optionally repeating this process using one or more of the product strings as an initial string in the collection of initial character strings.

Abstract: An apparatus for analyzing mass spectrometric data is described. The apparatus has a first input section for entering first data of an ion measured by mass spectrometry, a second input section for entering second data of a dissociated ion of the ion measured by mass spectrometry, a first data storing section for storing third data of mass spectrometry of a plurality of candidates for the structure of ion, a calculation section for producing fourth data of mass spectrometry of dissociated ions to be used in analyzing the plurality of candidates and an evaluation section for evaluating the plurality of candidates by making comparisons between the first and third data and between the second and fourth data, so that the structure of ion can be identified.

Abstract: This invention is directed to Acyl Carrier Protein Synthase (ACPS) crystals and crystals of Acyl Carrier Protein Synthase-Coenzyme A (ACPS-CoA) complex, and to the use of these crystals to determine the three dimensional structure of ACPS. This invention is further directed to the use of rational drug design methods to identify agents that may interact with active sites of ACPS and ACPS-CoA complex, and to the testing of these agents to identify agents that may inhibit ACPS and/or ACPS-CoA complex activity.

Abstract: Method and apparatus for detecting a selected material in a sample are disclosed. In the method, the sample is placed adjacent a detector coil, for generating an electromagnetic time-domain signal composed of sample source radiation. The signal is first conditioned to convert the signal to an amplified conditioned signal from which frequency components above a selected frequency have been removed, then filtered to selectively pass low-frequency spectral components that are (i) in a frequency range between dc and 50 khz, and (ii) characteristic of the selected material. The filtered signal is cross-correlated with a data set of low-frequency spectral components that are (i) in a frequency range between dc and 50 khz, and (ii) characteristic of a selected material, to produce a frequency-domain spectrum in the frequency range within DC to 50 khz.

Abstract: The invention provides methods for producing high resolution crystals of ribosomes and ribosomal subunits as well as crystals produced by such methods. The invention also provides high resolution structures of ribosomal subunits either alone or in combination with protein synthesis inhibitors. The invention provides methods for identifying ribosome-related ligands and methods for designing ligands with specific ribosome-binding properties as well as ligands that may act as protein synthesis inhibitors. Thus, the methods and compositions of the invention may be used to produce ligands that are designed to specifically kill or inhibit the growth of any target organism.

Abstract: The present invention provides a method for monitoring degradation of Hb-based blood substitutes, in a sample. This method involves determining a concentration of met-Hb within the sample, by applying a calibration algorithm for met-Hb to an absorbance obtained from the sample at one or more than one wavelengths, and using the concentration of met-Hb, as a measurement of degradation of the Hb-based blood substitutes. Using this assay, a concentration of met-Hb that is equal to or greater than 3% may be used as an indicator of degradation of Hb. Alternatively, by obtaining samples over a period of time, the concentration of met-Hb and the concentration of Hb-based blood substitute may be determined in each of these samples, and an increase in the concentration of met-Hb over the period of time is an indicator of degradation of Hb.

Abstract: This invention relates to crystallization based assays for identifying ligands that bind to a macromolecule.

Abstract: The present invention relates to apparatus and methods for quantitative protein design and optimization.

Abstract: The invention relates to methods of identifying and characterizing properties of polymers to provide information about the polymer such as the charge of the polymer, the number and types or characteristics of units of the polymer and the sequence of the polymers. The invention also relates to methods of sequencing polymers such as nucleic acids, polypeptides and polysaccharides and methods for identifying a polysaccharide-protein interaction.

Abstract: Disclosed is are methods of generating chemical structures of putative non-peptide inhibitors of biologically-active receptors. The method includes constructing a model of a receptor-ligand complex using empirical three-dimensional data of the receptor-ligand complex. The conformation of the binding site between the receptor and the ligand is then altered to yield novel conformations not exhibited in either the native receptor or the bound receptor. These conformations are then used to generate models of non-peptide chemical structures that are complementary in structure to the altered conformations of the binding site. In this fashion, chemical structures of putative non-peptide inhibitors of the altered conformation are revealed.

Abstract: A method of identifying and unknown compound comprises: (a) obtaining an absorption spectrum of the compound; (b) obtaining an absorbance value An(?n) wherein An is the absorption value at a wavenumber ?n; (c) generating an array of values A?n(??n) wherein A?n(??n)=A?n(??n)?A? where A? is an absorbance value which is modified from the measured absorbance, such as Aavg where Aavg is the average of An(?n); (d) generating an array of values In(?n) by integrating A?n(??n) over a region of the spectrum; (e) normalizing the array of values In(?n) with values I?n(??n) obtained for a known compound. The system of this invention employs the above-described method in cooperation with a computer capable of receiving the absorption spectrum data and calculating values from the data using algorithms provided to the computer. The method and system of this invention may be used to identify unknown compounds for quality control, process control and other purposes.