Protein and nucleic acid are important cellular macromolecules. All cellular processes(signal transduction, cell response to extracellular and intracellular environmental change)depend on precise interactions mediated by proteins. Protein-nucleic acid interaction is central question in molecular biology. Despite progress in macromolecules interaction research, the description of the interactome represents one of key challenges remaining for structural biology. Cooperation in multi-knowledge based on biology, chemistry, physics and computer are considerable for further research. We focus on two crucial protein in organisms: NAD+ dependent DNA ligase and PTB (polypyrimidine-tract binding protein) protein and elucidate the interaction of these complex. We reveal the characteristic on the protein-nucleic acid recognition and the sequence-structure-function relationships in the two interaction system. DNA ligases belong to the covalent nucleotidyltransferases. DNA ligases catalyze the joining of nicked DNA, which is necessary in DNA replication and repair pathways where the re-synthesis of DNA is required. DNA ligase is an ancestral and crucial enzyme. Most organisms use ATP powered DNA ligases, but eubacteria appear to be uniquely use ligases driven by NAD+. Hitherto, it is not clear understand how the ligases recognize DNA. In the former part of this work, we report for the first time, three novel motifs unique in NAD+ dependent DNA ligase are not defined in previous studies. A highly automated calculation for non-bonded energy approach is created. It calculates the non-bonded interaction energies between the residues in the motifs and bases in DNA. The result shows that the major contribution for the recognition of ligase-DNA is the residues which in the motifs: Arginine136 (motif A), Arginine200 (motif B), Arginine333 (motif C). Only three motifs previous definition show high interaction. A DNA nick recognition model for the DNA ligases was proposed and can explain DNA ligase biding in all available complexs. Another part of this work is to study binding affinity and molecular basis for CU-rich RNA recognition in PTB protein. PTB（Polypyrimidine tract binding protein） is observed in eukaryote ubiquitously. Function of PTB protein is its role as a regulator of alternative splicing. PTB protein preferentially binds pyrimidine-tract containing CU-rich tracts, the mechanism is unknown. Our analysis shows that serine and vicinal plar residues which located beta4-strand of RRM domain play crucial role to binding RNA. It is novel site.The customize Pipeline Pilot Protocols has been set up, which can calculate the binding free energy of complexes based on MM/PBSA method. We create mutant by conseved residues in beta4 and calculated each binding free energy. Compared to the wt PTB protein binding free energy, we find that, mutant increased the energy largely. Dynamic ananlysis show that hydrogen bond is crucial for specific bind to C pyrimidin. In addition, we develop module based on DS. Three strategys was considered. Firstly, we integrate Perl code into DS menue, and run in DS windows. Secondly, we create protocol by Pipeline Pilot and import to Discovery Studio. Thirdly, accessible the DS programming interface by Perl code and run from the command line without open the DS client windows. The extension module applies to our analysis of protein- nucleic acid complex.
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