| A drug has been designed to bind specific subsets of DNA sequences. The monoimidazole lexitropsin was intended to distinguish between AT and GC base pairs. However, the crystal structure of the DNA-drug complex reveals that the lexitropsin is an indiscriminate binder. Its two positively charged tails draw it into the negative electrostatic potential of deep minor grooves associated with AT-rich sequences.; The relationship between DNA sequence and structure is also demonstrated in the first crystal structure of an A/B-DNA intermediate. Guanine rich sequences have long been known to facilitate the transition of B DNA to A DNA. The sequence CATGGGCCCATG, with three consecutive guanines, crystallizes as an A/B-DNA intermediate. In contrast, the similar sequence CATGGCCATG, with two consecutive guanines, crystallizes as B DNA. This unusual structure is examined by quantum mechanics ab initio calculations, solvation simulation, and molecular dynamics simulations. The properties of this intermediate favor the Calladine-Drew “Slide first, roll later” pathway for the B → A DNA transition. Energetic calculations suggest that DNA is a much more dynamic molecule than many have assumed.; In the post-genomic era, new bioinformatics tools are needed to take advantage of our newfound wealth of data. We have developed an algorithm that predicts protein functions and protein-protein interactions. The Rosetta Stone method relies on the correlation between protein function and genetic fusion events. Two proteins are more likely to be related in function if they can be found as a fused gene in an organism.; In many cases, proteins related in function share common structural or sequence elements. Actin binding proteins were searched for such motifs. Two motifs common to the villin headpiece, calponin homology, and gelsolin S1 domains were found. These motifs correlate with residues that had previously been determined to be critical for actin binding. |
