Abstract: Disclosed herein is a method of estimating the pose of a ligand in a receptor comprising identifying all possible atom pairs of protein-ligand complexes in a given configuration space for a system that comprises proteins; creating a first database and a second database; where the first database comprises associated pairwise distant dependent energies and where the second database comprises all probabilities that include how the atom pairs can combine; combining the first database with the second database via statistical mechanics to accurately estimate binding free energies as well as a pose of a ligand in a receptor; and selecting a protein-ligand complex for further study.

Abstract: Disclosed herein is a method of estimating the pose of a ligand in a receptor comprising identifying all possible atom pairs of protein-ligand complexes in a given configuration space for a system that comprises proteins; creating a first database and a second database; where the first database comprises associated pairwise distant dependent energies and where the second database comprises all probabilities that include how the atom pairs can combine; combining the first database with the second database via statistical mechanics to accurately estimate binding free energies as well as a pose of a ligand in a receptor; and selecting a protein-ligand complex for further study.

Abstract: Disclosed herein is a method of estimating the pose of a ligand in a receptor comprising identifying all possible atom pairs of protein-ligand complexes in a given configuration space for a system that comprises proteins; creating a first database and a second database; where the first database comprises associated pairwise distant dependent energies and where the second database comprises all probabilities that include how the atom pairs can combine; combining the first database with the second database via statistical mechanics to accurately estimate binding free energies as well as a pose of a ligand in a receptor; and selecting a protein-ligand complex for further study.

Abstract: The present invention provides for the first time a quantum mechanics-based method for scoring protein-ligand interactions and binding affinity predictions, using quantum mechanical Hamiltonians and/or a combined quantum mechanical/molecular mechanical approach, and Poisson-Boltzmann (PB)-based solvation methods. Also provided is a method for using quantum mechanics to describe the enthalpic and solvation effects of binding. The method comprises comparing the calculated binding affinities to experimental values in order to measure the success of the method. The methods disclosed herein may further be used to score protein and drug or protein and inhibitor interactions. The present method can predict the free energy of binding of protein-ligand complexes with high accuracy so as to enable lead optimization, thus serving as a powerful tool in computational drug design.

Abstract: Molecules are represented as one dimensional strings of atoms having a linear position and a width. One dimensional representations are compared to assess the likelihood of similarity in chemical behavior.

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: The present teachings describe a solubility prediction approach that is based, in part, upon quantitative-structure property relationships (QSPR). In various embodiments, the solubility prediction methodology comprises identifying a reduced descriptor set from which a solubility equation is derived. The descriptors used in the solubility equation are based upon simplified structural and molecular features which facilitate researcher understanding and solubility model refinement. Moreover, the present teachings provide solubility prediction relationships that may be used to rapidly screen large libraries or collections of compounds.

Abstract: A high-throughput molecular docking facility is presented for screening combinatorial libraries to identity binding ligands and ultimately pharmaceutical compounds. The facility employs a pre-coking conformational search to generate multiple solution conformations of a ligand. The molecular docking facility includes: generating a binding site image of the target molecule, 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 postion relative to the target molecule in a ligand-target molecule 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 target molecule fixed. Docking results are clustered using as a metric the rms deviation between the core of two docked molecules.

Abstract: Molecules are represented as one dimensional strings of atoms having a linear position and a width. One dimensional representations are compared to assess the likelihood of similarity in chemical behavior.

Abstract: The present teachings describe a solubility prediction approach that is based, in part, upon quantitative-structure property relationships (QSPR). In various embodiments, the solubility prediction methodology comprises identifying a reduced descriptor set from which a solubility equation is derived. The descriptors used in the solubility equation are based upon simplified structural and molecular features which facilitate researcher understanding and solubility model refinement. Moreover, the present teachings provide solubility prediction relationships that may be used to rapidly screen large libraries or collections of compounds.

Abstract: In a computational method of assessing a combinatorial library for complementarity to a target molecule, ligands from the library are first docked to the target molecule. The docking results are clustered using as a metric the rms deviation between the core of two docked molecules. The library is rated as to complementarity to the target molecule according to the relative number of ligands in the top cluster.

Abstract: A thick film temperature sensitive device and method of making the same, comprising the steps of applying to the surface of a substrate and firing a resistance material comprising a mixture of glass frit and particles containing palladium and iron. The mixture is fired in a non oxidizing, neutral, or reducing atmosphere at a temperature between 700.degree. C. and 1100.degree. C. at which the glass frit softens. When cooled, a device is provided with a glass film strongly bonded to the substrate and having dispersed therein conductive metal particles of an alloy of palladium and iron. The device provides a relatively high positive temperature coefficient of resistance, a relatively high resistivity, and a resistance to temperature characteristic which is highly linear, and can be processed by spiralling and terminated by the use of electroless plating.

Abstract: A vitreous enamel resistor material comprising a mixture of a vitreous glass frit and fine particles of tin oxide (SnO.sub.2). An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature between about 850.degree. C. and 1150.degree. C. at which the glass melts. Upon cooling, the substrate has on the surface thereof, a film of the glass having the particles of the tin oxide embedded therein and dispersed therethroughout. The resistor material provides a resistor having a resistivity within a wide range and a low temperature coefficient of resistance.

Abstract: A vitreous enamel resistor material comprising a mixture of a vitreous glass frit and fine particles of tin oxide (SnO.sub.2). An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature at which the glass melts. The tin oxide is preferably heat treated prior to mixing with the glass frit. Upon cooling, the substrate has on the surface thereof, a film of the glass having the particles of the tin oxide embedded therein and dispersed therethroughout. The resistor material provides a resistor having a wide range of resistivity and a low temperature coefficient of resistance.

Abstract: A vitreous enamel resistor material comprising a mixture of a vitreous glass frit and fine particles of tin oxide (SnO.sub.2). An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature at which the glass melts. The tin oxide is preferably heat treated prior to mixing with the glass frit. Upon cooling, the substrate has on the surface thereof, a film of the glass having the particles of the tin oxide embedded therein and dispersed therethroughout. The resistor material provides a resistor having a wide range of resistivity and a low temperature coefficient of resistance.

Abstract: A liquid level sensing means for providing a continuous indication of liquid level or liquid content of a container comprising an elongated light conducting element adapted for being received into a liquid having first and second ends and a surface which provides an interface with the liquid for measuring liquid levels between the ends of the conducting element. A source provides radiation to the conducting element at one end, and detecting means for sensing radiation transmitted by the conducting element is positioned at the end of the conducting element opposite to the source of radiation and provides an output signal responsive to the intensity of the sensed radiation. The conducting element is transparent to radiation, has an index of refraction which is greater than that of the liquid which is to have its level measured, and has contoured regions on at least a portion of its surface.

Abstract: A signal transducing unit which is compact and can be calibrated from outside its housing to provide zero and span adjustments after assembly with the components secured within its housing. The device has a pair of first and second elements movable with respect to each other and each having first and second ends and a conductive path, and the conductive paths of the elements electrically contact each other at a location which is displaced along their paths with the relative movement of the elements. Positioning means retains the elements for relative movement, while actuating means displaceable for moving and positioning the first element with respect to the first element controls the contact location of the elements.

Abstract: A vitreous enamel resistor material comprising a mixture of a glass frit, and fine particles of tin oxide (SnO.sub.2), a primary additive of particles of oxides of manganese, nickel, cobalt or zinc, and a supplemental additive of oxides of tantalum, niobium, tungsten or nickel. An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature at which the glass melts. The tin oxide may be heat treated prior to mixing the glass frit. Upon cooling, the substrate has on the surface thereof, a film of the glass having the particles of the mixture embedded therein and dispersed therethroughout. The resistor material provides a resistor having a wide range of resistivities and a low temperature coefficient of resistance.

Abstract: A vitreous enamel resistor material comprising a mixture of a vitreous glass frit and fine particles of tantalum. The vitreous enamel resistor material may also include fine particles selected from titanium, boron, tantalum oxide (Ta.sub.2 O.sub.5), titanium oxide (TiO), barium oxide (BaO.sub.2), zirconium dioxide (ZrO.sub.2), tungsten trioxide (WO.sub.3), tantalum nitride (Ta.sub.2 N), titanium nitride (TiN), molybdenum disilicide (MoSi.sub.2), and magnesium silicate MgSiO.sub.3). An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature at which the glass melts. Upon cooling, the substrate has on a surface thereof a film of glass having the tantalum particles and particles of the additive material, if used, embedded therein and dispersed therethroughout.

Abstract: A vitreous enamel resistor material comprising a mixture of a vitreous glass frit and fine particles of tantalum nitride (Ta.sub.2 N). The vitreous enamel resistor material may also include fine particles selected from boron, tantalum, silicon, zirconium dioxide (ZrO.sub.2), and magnesium zirconate (MgZrO.sub.3). An electrical resistor is made from the resistor material by applying the material to a substrate and firing the coated substrate to a temperature at which the glass melts. Upon cooling, the substrate has on a surface thereof a film of glass having the tantalum nitride particles and particles of the additive material, if used, embedded therein and dispersed therethroughout.