The present invention relates to polypeptide fragments comprising an amino-terminal fragment of the PA subunit of a viral RNA-dependent RNA polymerase or variants thereof possessing endonuclease activity, wherein said PA subunit is from a virus belonging to the Orthomyxoviridae family. This invention also relates to (i) crystals of the polypeptide fragments which are suitable for structure determination of said polypeptide fragments using X-ray crystallography and (ii) computational methods using the structural coordinates of said 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 identifying compounds that bind to the PA polypeptide fragments possessing endonuclease activity and preferably inhibit said endonucleolytic activity, preferably in a high throughput setting. This invention also relates to compounds and pharmaceutical compositions comprising the identified compounds for the treatment of disease conditions due to viral infections caused by viruses of the Orthomyxoviridae family.

A composition-of-matter comprising a crystallized form of a large ribosomal (50S) subunit of a pathogenic bacterium, and the atomic coordinates of the three-dimensional structure thereof are provided herein, as well as methods for crystallizing the same, and using the atomic coordinates of the same to design de novo ligands with high specificity thereto.

A computer-readable recording medium storing a feature amount calculation program for causing a computer to execute processing including: receiving structure specifying information indicating a type of each of atomic groups and a sequence of the atomic groups regarding a cyclic molecule in which the atomic groups classified into a plurality of types is cyclically sequenced; specifying an optional first type and an optional second type in the plurality of types; specifying, based on the structure specifying information, one or more of first atomic groups classified into the first type and one or more of second atomic groups classified into the second type out of the atomic groups; and calculating, based on the structure specifying information, a number of pairs of the first atomic group and the second atomic group in which a mutual distance in the sequence between the first atomic group and the second atomic group is a distance.

A computer-readable recording medium storing a feature amount calculation program for causing a computer to execute processing including: receiving structure specifying information indicating a type of each of atomic groups and a sequence of the atomic groups regarding a cyclic molecule in which the atomic groups classified into a plurality of types is cyclically sequenced; specifying an optional first type and an optional second type in the plurality of types; specifying, based on the structure specifying information, one or more of first atomic groups classified into the first type and one or more of second atomic groups classified into the second type out of the atomic groups; and calculating, based on the structure specifying information, a number of pairs of the first atomic group and the second atomic group in which a mutual distance in the sequence between the first atomic group and the second atomic group is a distance.

Computational systems and methods are described for identifying new α-helical antimicrobial peptides using a systemic consensus formula. Newly identified α-helical antimicrobial peptides are tested experimentally and show potent microbiocidal activities.

Computational systems and methods are described for identifying new α-helical antimicrobial peptides using a systemic consensus formula. Newly identified α-helical antimicrobial peptides are tested experimentally and show potent microbiocidal activities.

The present disclosure relates to a method for generating variants of a protein based on a native protein regulated by allosteric pathway, the method comprising: i) providing 3D structures of the native protein; ii) identifying at least one pair of coupled allosteric sites within the amino acid sequence of the native protein named microswitch; iii) generating in silico mutations of said identified microswitch to generate a pool of variants; iv) computing at least one score reflecting the variation in allosteric coupling; and/or the variation in the relative stability v) predicting the activity of each variant compared to the native protein based on the computed score. The disclosure also concern a computer implemented program to carry out said method, and a variant of a protein or an active fragment thereof, a polynucleotide.

The present disclosure relates to a method for generating variants of a protein based on a native protein regulated by allosteric pathway, the method comprising: i) providing 3D structures of the native protein; ii) identifying at least one pair of coupled allosteric sites within the amino acid sequence of the native protein named microswitch; iii) generating in silico mutations of said identified microswitch to generate a pool of variants; iv) computing at least one score reflecting the variation in allosteric coupling; and/or the variation in the relative stability v) predicting the activity of each variant compared to the native protein based on the computed score. The disclosure also concern a computer implemented program to carry out said method, and a variant of a protein or an active fragment thereof, a polynucleotide.

Disclosed is a method for improving affinity of an antibody for an antigen, comprising, in an unmodified antibody, improving affinity for an antigen as compared to the unmodified antibody, by changing 17th, 18th and 20th amino acid residues of a light chain defined by Kabat method to charged amino acid residues.

This invention relates to the identification of peptide binding to ligands, and in particular to identification of epitopes expressed by microorganisms and by mammalian cells. The present invention provides polypeptides comprising the epitopes, and vaccines, antibodies and diagnostic products that utilize or are developed using the epitopes.