The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.

The present invention relates to a method of predicting the propensity of tripeptides to from aggregates in solution. The present invention also provides tripeptides which are able to form aggregates in solution, as well as uses thereof. The present invention also provides nanostructures formed by self-aggregation of tripeptides of the present invention. The present invention also provides pH responsive aggregates as well as methods of screening for the ability of a tripeptide to form a pH dependent aggregate or gel.

A protein composition including TorsinA or TorsinA mutant, LULL1, and a nanobody obtained by immunization using TorsinA and LULL1 is used to grow complex crystals, and three dimensional structures are determined using x-ray data of the crystals. A creening platform is built based on the determined three dimensional structures for designing a drug lead to cure dystonia.

The invention is a diagnostic which overlays quantum mechanical analysis to x-ray crystallography data from one or more proteins to assess and identify the real world conformation, protonation and solvent effects of one or more moieties in said protein. This “overlay” occurs by scoring and identifying the protomer/tautomer states of the moieties using quantum mechanical analysis. The diagnostic results of the present invention accurately identify protein-ligand binding, rendered as an output to a user of a computer in which the x-ray crystallography data is analysed with semi-empirical Hamiltonian quantum mechanics and

The present invention relates to enzyme inhibitors. More specifically, the present invention relates to ligand-directed covalent modification of proteins; method of designing same; pharmaceutical formulation of same; and method of use.

Methods involving the use of mathematical models of competitive ligand-receptor binding to characterize mixtures of ligands in terms of compositions and properties of the component ligands have been developed. The associated mathematical equations explicitly relate component ligand physical-chemical properties and mole fractions to measurable properties of the mixture including steady state binding activity, 1/K.sub.d,apparent or equivalently 1/EC50, and kinetic rate constants k.sub.on,apparent and k.sub.off,apparent allowing; 1) component ligand physical property determination and 2) mixture property predictions. Additionally, mathematical equations accounting for combinatorial considerations associated with ligand assembly are used to compute ligand mole fractions. The utility of the methods developed is demonstrated using published experimental ligand-receptor binding data obtained from mixtures of afucosylated antibodies that bind FcγRIIIa (CD16a) to: 1) extract component ligand physical property information that has hitherto evaded researchers 2) predict experimental observations and 3) provide explanations for unresolved experimental observations.

The present invention provides polypeptides and compositions thereof for treating or limiting respiratory syncytial virus infection, and computational methods for designing such polypeptides.

Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are converted to inhibitors of GSK-3 upon interacting with the enzyme's catalytic site and hence act as disease-selective inhibitors for treating conditions associated with increased activity and/or expression of GSK-3. Each of the disclosed peptides is independently of no more than 15 amino acid residues, and has an amino acid sequence which comprises a ZX.sub.1X.sub.2X.sub.3Z(p) recognition motif of GSK-3, wherein Z(p) is a phosphorylated serine or threonine residue; Z is a phosphorylatable serine or threonine residue, and each of X.sub.1, X.sub.2 and X.sub.3 is independently any amino acid, as defined in the specification. Further disclosed are methods of identifying a putative substrate-competitive peptide inhibitor of GSK-3 which are effected by computational modeling and screening.

Systems and methods are disclosed for using geometry sensitivity information for guiding workflows in order to produce reliable models and quantities of interest. One method includes determining a geometric model associated with a target object; determining one or more quantities of interest; determining sensitivity information associated with one or more subdivisions of the geometric model and the one or more quantities of interest; and generating, using a processor, a workflow based on the sensitivity information.

A computer system crawls a plurality of web pages; parses the crawled information into state events and determines causality between any two of the state events; and stores the state events and the causality in a database. The system receives a first request from a user to determine a path to a target state. The system obtains a current state of the user. The system determines one or more paths from the current state of the user to the target state based on the current state of the user and the state events and the causality, including identifying one or more recommended state events, each recommended state event having a causality value for the target state that satisfies first preselected causality criteria; and provides at least one path from the current state of the user to the target state.