Abstract: A method of enhancing p53 activity of a p53 mutant polypeptide is provided. The method includes interacting a compound to an open L1/S3 binding site of the p53 mutant polypeptide, where the p53 activity of the p53 mutant polypeptide is enhanced in the presence of the compound. Compounds were identified from databases of compounds for virtual drug screening. Methods of screening for compounds that enhance p53 activity by binding to the open L1/S3 binding site, and methods of treatment using the identified compounds, are also provided.

Abstract: A method of enhancing p53 activity of a p53 mutant polypeptide is provided. The method includes interacting a compound to an open L1/S3 binding site of the p53 mutant polypeptide, where the p53 activity of the p53 mutant polypeptide is enhanced in the presence of the compound. Compounds were identified from databases of compounds for virtual drug screening. Methods of screening for compounds that enhance p53 activity by binding to the open L1/S3 binding site, and methods of treatment using the identified compounds, are also provided.

Abstract: Methods are provided for making a circular duplex polynucleotide. Such methods can include providing a mixture of sequence specific linear duplex polynucleotides and denaturing and reannealing the polynucleotide mixture under conditions such that some of the polynucleotides form circular duplexes that comprise the desired polynucleotide.

Abstract: Provided herein are isolated polynucleotides encoding collagen-like polypeptide domains and the encoded polypeptides. In one such polypeptide, at least a portion of the encoded collagen-like polypeptide domain is in the form of Gly-X-Y triads, where X and Y symbolize individual amino acids; X is proline in at least 20% of the triads; Y is proline in at least 20% of the triads. The encoding polynucleotide of such a polypeptide encodes a region having at least 50 consecutive amino acids, wherein the region is at least 90% identical to an amino acid sequence of a naturally occurring collagen polypeptide; and no more than 98% of the nucleotides of the collagen-like polypeptide domain-encoding portion of the polynucleotide fall into a window of 100 consecutive nucleotides in which the nucleotides of the window have greater than 98% identity to a naturally occurring collagen-encoding nucleotide sequence.

Abstract: Disclosed herein is a method for synthesizing a desired nucleic acid sequence. The method comprises dividing the desired sequence into a plurality of partially overlapping segments; optimizing the melting temperatures of the overlapping regions of each segment to disfavor hybridization to the overlapping segments which are non-adjacent in the desired sequence; allowing the overlapping regions of single stranded segments which are adjacent to one another in the desired sequence to hybridize to one another under conditions which disfavor hybridization of non-adjacent segments; and filling in, ligating, or repairing the gaps between the overlapping regions, thereby forming a double-stranded DNA with the desired sequence. Also disclosed is a method for preventing errors in the synthesis of the nucleic acid sequence.

Abstract: Disclosed herein is a method for synthesizing a desired nucleic acid sequence. The method comprises dividing the desired sequence into a plurality of partially overlapping segments; optimizing the melting temperatures of the overlapping regions of each segment to disfavor hybridization to the overlapping segments which are non-adjacent in the desired sequence; allowing the overlapping regions of single stranded segments which are adjacent to one another in the desired sequence to hybridize to one another under conditions which disfavor hybridization of non-adjacent segments; and filling in, ligating, or repairing the gaps between the overlapping regions, thereby forming a double-stranded DNA with the desired sequence. Also disclosed is a method for preventing errors in the synthesis of the nucleic acid sequence.

Abstract: Explicit representation of molecular shape of molecules is combined with neural network learning methods to provide models with high predictive ability that generalize to different chemical classes where structurally diverse molecules exhibiting similar surface characteristics are treated as similar. A new machine-learning methodology is disclosed that can accept multiple representations of objects and construct models that predict characteristics of those objects. An extension of this methodology can be applied in cases where the representations of the objects are determined by a set of adjustable parameters. An iterative process applies intermediate models to generate new representations of the objects by adjusting said parameters and repeatedly. retrains the models to obtain better predictive models. This method can be applied to molecules because each molecule can have many orientations and conformations (representations) that are determined by a set of translation, rotation and torsion angle parameters.