Interactions between the aromatic amino acid residues have a significant influence on the protein structures and protein-DNA complexes. These interactions individually provide little stability to the structure; however, together they contribute significantly to the conformational stability of the protein structure. In this study, we focus on the four aromatic amino acid residues and their interactions with one another and their individual interactions with the four nucleotide bases. These are analyzed in order to determine the extent to which their orientation and the number of interactions contribute to the protein and protein-DNA complex structures.

Rv0045c is an esterase involved in lipid metabolism of Mycobacterium tuberculosis. It belongs to the α/β hydrolase family. In the current study, we performed sequence- and structure-based analysis of Rv0045c followed by molecular dynamics (MD) simulation for 100 ns to investigate conformational changes in the enzyme. Sequence analysis revealed that this enzyme is possibly a hormone-sensitive lipase. Further, through structural analysis, a putative catalytic tetrad containing "Ser-Asp-Ser-His" and residues involved in the formation of an oxyanion hole were identified. MD simulation of Rv0045c revealed a conformational transition from an open to a closed state. The active site pocket was found to be gated by four loops. The potential role of the cap domain and the mobile histidine is discussed. From the simulation, we see that the conformational changes mimic the different stages in the reaction mechanism of Rv0045c. These results support the hypothesis that free enzyme simulation encompasses all the conformations necessary for the different stages of catalysis. Our findings add to the growing knowledge of an important family of esterases in Mycobacterium tuberculosis.

The function of a protein molecule is greatly influenced by its three-dimensional (3D) structure and therefore structure prediction will help identify its biological function. We have updated Sequence, Motif and Structure (SMS), the database of structurally rigid peptide fragments, by combining amino acid sequences and the corresponding 3D atomic coordinates of non-redundant (25%) and redundant (90%) protein chains available in the Protein Data Bank (PDB). SMS 2.0 provides information pertaining to the peptide fragments of length 5-14 residues. The entire dataset is divided into three categories, namely, same sequence motifs having similar, intermediate or dissimilar 3D structures. Further, options are provided to facilitate structural superposition using the program structural alignment of multiple proteins (STAMP) and the popular JAVA plug-in (Jmol) is deployed for visualization. In addition, functionalities are provided to search for the occurrences of the sequence motifs in other structural and sequence databases like PDB, Genome Database (GDB), Protein Information Resource (PIR) and Swiss-Prot. The updated database along with the search engine is available over the World Wide Web through the following URL http://cluster.physics.iisc.ernet.in/sms/.

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