A method of making a polypeptide including at least one covalent bond between a pair of reactive side chains of corresponding amino acids, wherein the covalent bond is insensitive to reduction is provided including genetically modifying a genomically recoded organism to express a corresponding synthetase, tRNA or synthetase/tRNA pair for translating mRNA encoding the corresponding amino acids having the reactive side chains into the polypeptide and to express the polypeptide including the at least one pair of the reactive side chains wherein the reactive side chains are oriented near one another when the expressed polypeptide is in a folded configuration, wherein the reactive side chains react to form the covalent bond that is insensitive to reduction.

Computational methods for classifying and predicting protein side chain conformations utilizing a data driven scoring function are disclosed. According to some embodiments, the methods may include obtaining structure data representing a plurality of conformations of a compound. The methods may also include determining structural differences among the conformations. The methods may also include classifying, based on the structural differences, the conformations into one or more clusters. The methods may also include determining representative conformations of the dusters, wherein an average structural difference between a representative conformation of a duster and conformations in the duster is below a predetermined threshold. The method may further include determining the representative conformations as poses of the compound.

The invention provides a novel integrated structure and system-based approach for drug target prediction that enables the large-scale discovery of new targets for existing drugs Novel computer-readable storage media and computer systems are also provided. Methods and systems of the invention use novel sequence order-independent structure alignment, hierarchical clustering, and probabilistic sequence similarity techniques to construct a probabilistic pocket ensemble (PPE) that captures even promiscuous structural features of different binding sites for a drug on known targets. The drug's PPE is combined with an approximation of the drug delivery profile to facilitate large-scale prediction of novel drug-protein interactions with several applications to biological research and drug development.

The present invention relates to a medicament design pocket of ODC. Based on the crystal structure of human ODC, the binding site area of putrescine and PLP ligand on the ODC homodimer interface is the medicament pocket, which is used for screening or designing or modifying inhibitors of human ODC, or screening or designing or modifying inhibitors of non-human ODC, or screening or designing or modifying protein inhibitor highly homologous to the binding site of putrescine and pyridoxal phosphate on the interface of ODC homodimer. The invention also provides the structure of the inhibitor and its application thereof. The technical solutions in the invention provide reliable theoretical basis for the research and development of human ODC, the prevention, treatment and diagnosis of tumors and pathogenic microbial infections, and the research and development and preparation of medicaments for the treatment of tumors or pathogenic microbial infections.

Hybrid alpha-amylases are provided that share a conserved 3D structure in whole or in part with a wild-type Termamyl-like α-amylase, e.g., a Bacillus amylase. In the hybrid, an N-terminal portion of a Termamyl-like α-amylase is replaced with sequences from an archae α-amylase. The sequence similarity between the two amylase sequences may be less than 60%. Conserving the wild-type 3D structure in the hybrid facilitates obtaining enzymatically active amylases. In one embodiment, one or both amylase sequences contribute residues to the B domain, resulting in particularly advantageous properties. For instance, replacement of the Ca.sup.2+ binding site in the B domain of the Termamyl-like α-amylase with a B domain sequence of an archae α-amylase that does not bind Ca.sup.2+ can produce a hybrid that is fully active in the absence of Ca.sup.2+.

Methods of identifying RNA-protein interaction sites are provided. Systems for identifying RNA-protein interaction sites are provided. Systems for identifying secondary structures are provided. Methods of identifying secondary structures are provided. Methods of identifying RNA-binding proteins are provided.

The present disclosure provides a protein complex, including a three-dimensional structure of the protein complex, that plays a role in regulation of body weight. In addition, the protein complex and components thereof, including three-dimensional structures thereof, find use in identifying agents that can be used to control body weight.

The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase possessing endonuclease activity, wherein the PA subunit is from Influenza A 2009 pandemic H1N1 virus or is a variant thereof. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of the polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of the polypeptide to screen for and design compounds that modulate, preferably inhibit the endonucleolytically active site within the polypeptide fragment. In addition, this invention relates to methods of identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit the endonucleolytic activity, as well as the compounds themselves. Preferably, the compounds are identifiable by the methods disclosed herein or the pharmaceutical compositions are producible by the methods disclosed herein.

A method of making a synthetic foldable having a tertiary structure emulating the tertiary structure of a reference foldable protein is described. The method includes determining a folding nucleus peptide sequence associated with folding the reference foldable protein. The synthetic foldable protein is synthesized by including the determined folding nucleus peptide sequence and at least one repeat thereof in the peptide sequence of the synthetic foldable protein.

The present patent relates to a method for qualitative identification and quantitative prediction of thyroid hormone disrupting chemicals base on the interaction between thyroid hormone receptor and co-regulators (coactivator and corepressor).The method identifies chemicals as passive antagonists, active antagonists and agonists by means of co-regulator involved molecular dynamics simulations, and predicts the relative disrupting potencies by use of binding free energy, therefore, may be used for screening of thyroid hormone disruptors among environmental pollutants. Upon more comprehensive consideration of the functioning mechanism of thyroid hormone receptor, the present invention is able to sufficiently identify thyroid hormone disruptors as agonists and antagonists, and gives more accurate prediction of the disrupting potency. Further, since nuclear receptors, just as thyroid hormone receptor, are strongly associated with co-regulators, the method may be expanded to the screening of nuclear receptor mediated endocrine disruptors.