The present invention is directed to systems and methods for fast and accurate structural representation and comparison of proteins. Specifically, the present invention provides a method for retrieval of a candidate set of near structural neighbors or structurally similar proteins of a query protein. The method is based on a representation of a protein structure as a “bag of words”—a collection of small disjoint backbone protein fragments. The representation allows quick comparison procedures of the query protein structure to a large number of known protein structures obtained for example, from a repository or database of proteins.

The present invention relates to a method for modeling the geometric structure of the interface of Receptor-Ligand complexes, a method for modeling the interaction between a Receptor and a Ligand in Receptor-Ligand complexes, a method for determining a scoring vector w which is a mathematical vector quantifying and/or qualifying the interaction of a geometric structure of the interface of a Receptor-Ligand complex, a method for determining the binding affinity or binding free energy of a position of a Ligand relative to a Receptor in one or more Receptor-Ligand complexes, and a method for ranking the binding affinity or binding free energy of spatial positions of a Ligand relative to a Receptor in one or more Receptor-Ligand complexes.

The present invention provides a system and method for extracting elements from distributed arrays on a parallel processing system. The system includes a module that populates a result array with globally largest elements from input arrays, a module that generates a partition element, a module that counts the number of local elements greater than the partition element, and a module that determines the globally largest elements. The method for extracting elements from distributed arrays on a parallel processing system includes populating a result array with globally largest elements from input arrays, generating a partition element, counting the number of local elements greater than the partition and determining the globally largest elements.

Methods for treating cancer using compounds that inhibit human DNA ligases. Methods for using compounds that inhibit human DNA ligases to provide insights into the reaction mechanisms of human DNA ligases, for example to identify the human DNA ligase involved in different DNA repair pathways. Screening methods for compounds that inhibit human DNA ligases.

Compositions and methods of treating an inflammatory disease in a subject are provided. Accordingly there is provided a method comprising administering to the subject a therapeutically effective amount of an agent which selectively inhibits activity and/or expression of iron regulatory protein (IRP) 1 and not IRP2, thereby treating the inflammatory disease in the subject. Also provided is a pharmaceutical composition comprising, as an active ingredient, an agent which selectively inhibits activity and/or expression of IRP1 and not IRP2, and a pharmaceutically acceptable carrier or excipient. Also provided are methods of identifying an agent that selectively modulates an activity of an IRP member of an IRP family of polypeptides and not of an additional IRP member of said IRP family of polypeptides.

A method for linking a natural product and gene cluster is disclosed. In some embodiments, monomers of natural products are predicted from a gene sequence. In other emboidments, monomers of natural products are predicted from a chemical structure of a natural product. In another embodiment, monomers predicted from gene sequences are aligned with monomers predicted from chemical structures.

A method is described for the identification of multi-subunit biocomplex drug targets. The method includes identifying a target that performs a biological function, wherein the target comprises one or more subunits, wherein a minimum number of the one or more subunits is inactivated to inhibit the biological function. The method includes selecting a drug that binds specifically to each subunit of the one or more subunits with a target probability. The method describes a relationship between inhibition efficiency of the drug and total number of the one or more subunits using a binomial distribution, wherein the inhibition efficiency comprises a probability that the delivered drug blocks the biological function. The method includes confirming empirically the relationship using an experimental target. The method includes administering the drug to the target to treat a multi-drug resistant disease, wherein the target comprises a biological complex in a mammalian subject.

The invention is a high-throughput voltage screening crystallographic device and methodology that uses multiple micro wells and electric circuits capable of assaying different crystallization condition for the same or different proteins of interest at the same of different voltages under a humidity and temperature controlled environment. The protein is solubilized in a lipid matrix similar to the lipid composition of the protein in the native environment to ensure stability of the protein during crystallization. The invention provides a system and method where the protein is transferred to a lipid matrix that holds a resting membrane potential, which reduces the degree of conformational freedom of the protein. The invention overcomes the majority of the difficulties associated with vapor diffusion techniques and essentially reconstitutes the protein in its native lipid environment under cuasi physiological conditions.

Disclosed herein is a method for verifying the primary structure of a protein through comparative analyses between ion clusters observed in mass spectra and a series of simulated ion clusters deduced from its putative chemical formula. The method comprises the steps of: preparing a protein sample for mass spectrometric analyses; collecting mass spectra of the protein sample; obtaining master ion cluster from a plurality of ion clusters in the mass spectra; producing a series of simulated ion clusters according to the chemical formula of the protein; finding the best fit for the master ion cluster among the series of simulated ion clusters; and verifying if said best-fit simulated ion cluster corresponds to the chemical formula of the protein.

Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.