This project involves the use of DOCK 3.5 to identify small molecules that bind to a particular DNA structure. This structure is a quadruple helix which forms base quadruples through Hoogsteen base-pairing of four guanidine nucleotides. The particular structure being examined is a dimer of two oligonucleotides, each consisting of 12 nucleotides in the sequence (GGGGTTTTGGGG). DOCK is a software package that screens a database of small molecules to identify candidates that bind to a particular macromolecular site. The selection of the small molecules is based on geometric complementarity with the binding site. DOCK also allows for chemical complementarity of the candidates to be evaluated through the use of the AMBER force field. Another project involves changing the chemical scoring to better account for hydrogen bonds. The use of DOCK involves characterizing the binding site, executing the database search, and finally scrutinizing the list of candidates for those with the most potential for further study. Computer graphics are essential at several points during a DOCK run. First, the characterization of the binding site is aided greatly by a graphical interface. Specifically designating atoms that are to be used for the characterization requires computer graphics. Second, the characterization of the binding site must be checked graphically. Computer graphics allow the user to verify that the representation of the site generated by DOCK provides an accurate representation of the actual site. Finally, and most importantly, computer graphics are essential in examining the candidates produced by the search. This allows the user to ascertain what configuration of the small molecule in the binding site was generated by DOCK. By allowing the user to examine the molecule in this configuration and in the context of the binding site, computer graphics allow the knowledgeable user to make an evaluation of the prospects for binding.
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