A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (O.sup.A.sub.1-n), where n is at least one; defining a population (P.sub.G=0) of at least one molecule; selecting an initial population (P.sub.parent) of at least one molecule (I.sub.1-I.sub.n) from the population (P.sub.G=0); and evaluating members (I.sub.1-I.sub.n) of the initial population (P.sub.parent) against at least one of the n achievement objectives (O.sup.A.sub.1-x), where x is from 1 to n.

A method for computational drug design using an evolutionary algorithm, comprises evaluating virtual molecules according to vector distance (VD) to at least one achievement objective that defines a desired ideal molecule. In one method the invention comprises defining a set of n achievement objectives (O.sup.A.sub.1-n), where n is at least one; defining a population (P.sub.G=0) of at least one molecule; selecting an initial population (P.sub.parent) of at least one molecule (I.sub.1-I.sub.n) from the population (P.sub.G=0); and evaluating members (I.sub.1-I.sub.n) of the initial population (P.sub.parent) against at least one of the n achievement objectives (O.sup.A.sub.1-x), where x is from 1 to n.

The invention provides efficient methods for combining single-substitution libraries of nucleic acids that span and encode proteins of interest and for selecting resultant mutant proteins after expression which have improved properties or characteristics. Specifically, the methods comprising synthesizing a single substitution library for each of a plurality of domains of a protein; expressing separately each member of each single substitution library as a pre-candidate protein; selecting members of each single substitution library which encode pre-candidate proteins which exhibit an improvement in the one or more predetermined characteristics to form a selected library; shuffling members or the selected libraries in a PCR to produce a combinatorial shuffled library; expressing members of the shuffled library as candidate proteins; and selecting mutant proteins which have improved properties or characteristics.

The invention relates to a method for producing a ribonucleic acid (RNA) molecule composition comprising n different RNA molecule species, the method comprising a step of RNA in vitro transcription of a mixture of m different deoxyribonucleic acid (DNA) molecule species in a single reaction vessel in parallel, i.e. simultaneously, and a step of obtaining the RNA molecule composition. Also provided is the RNA composition provided by the inventive method and a pharmaceutical composition comprising the same as well as a pharmaceutical container. Moreover, the invention provides the RNA composition and the pharmaceutical composition for use as medicament.

Disclosed herein are engineered nucleases and nuclease systems, including chimeric nucleases and chimeric nuclease systems. Engineered and chimeric nucleases disclosed herein include nucleic acid guided nucleases. Additionally disclosed herein are methods of generating engineered nucleases and methods of using the same.

Disclosed herein are engineered nucleases and nuclease systems, including chimeric nucleases and chimeric nuclease systems. Engineered and chimeric nucleases disclosed herein include nucleic acid guided nucleases. Additionally disclosed herein are methods of generating engineered nucleases and methods of using the same.

Novel methods that may be used for the manufacture of plant alkaloid compounds and novel polynucleotide compounds are provided. The plant alkaloid compounds are useful as medicinal compounds.

A general method and recombinant nucleic acid sequences, by means which the method selects a recombinant protein containing an FHA domain for binding a target molecule from a library proteins with a high-throughput method of creating protein variations within the FHA domain in non-conserved or non-structural sequences of the FHA scaffold, and the library may also be in the form of a phagemid or phage library wherein the ALP nucleic acid sequence is inserted into a vector capable of allowing the vector and expressed ALP protein from being virally packaged, and the recombinant nucleic acid sequences which are randomly mutated at varying non-conserved or non-structural FHA domain sequences.

A general method and recombinant nucleic acid sequences, by means which the method selects a recombinant protein containing an FHA domain for binding a target molecule from a library proteins with a high-throughput method of creating protein variations within the FHA domain in non-conserved or non-structural sequences of the FHA scaffold, and the library may also be in the form of a phagemid or phage library wherein the ALP nucleic acid sequence is inserted into a vector capable of allowing the vector and expressed ALP protein from being virally packaged, and the recombinant nucleic acid sequences which are randomly mutated at varying non-conserved or non-structural FHA domain sequences.

Strategies, systems, methods, reagents, and kits for phage-assisted continuous evolution are provided herein. These include strategies, systems, methods, reagents, and kits allowing for stringency modulation to evolve weakly active or inactive biomolecule variants, negative selection of undesired properties, and/or positive selection of desired properties.