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About Laboratory Of Bioinformatics And Protein Engineering

Our group is involved in theoretical and experimental research on nucleic acids and proteins. The current focus is on RNA sequence-structure-function relationships (in particular 3D modeling), RNA-protein complexes, and enzymes acting on RNA.
 
We study the rules that govern the sequence-structure-function relationships in proteins and nucleic acids and use the acquired knowledge to predict structures and functions for uncharacterized gene products, to alter the known structures and functions of proteins and RNAs and to engineer molecules with new properties.
 
Our key strength is in the integration of various types of theoretical and experimental analyses. We develop and use computer programs for modeling of protein three-dimensional structures based on heterogenous, low-resolution, noisy and ambivalent experimental data. We are also involved in genome-scale phylogenetic analyses, with the focus on identification of proteins that belong to particular families. Subsequently, we characterize experimentally the function of the most interesting new genes/proteins identified by bioinformatics. We also use theoretical predictions to guide protein engineering, using rational and random approaches. Our ultimate goal is to identify complete sets of enzymes involved in particular metabolic pathways (e.g. RNA modification, DNA repair) and to design proteins with new properties, in particular enzymes with new useful functions, which have not been observed in the nature.
 
We are well-equipped with respect to both theoretical and experimental analyses. Our lab offers excellent environment for training of young researchers in both bioinformatics and molecular biology/biochemistry of protein-nucleic acid interactions.


More Good Science

Model of MiaA.
 
MiaA (E.C. 2.5.1.8) is a prenyltransferase, which is responsible for introducing posttranscriptional modification N6-(?2-isopentenyl)adenosine (i6A) in position 37 in tRNA. MiaA is related to P-loop NTPases, a large class of proteins with diverse structures and functions. At the stage of our researches no structural information about enzymes from this family was available. However, we constructed a structural model of EcMiaA (Escherichia coli MiaA enzyme) with a respect to known experimental data and predictions of fold-recognition methods. Not long after the acceptance of the final version of our manuscript [1], the crystal structure of BsMiaA (Bacillus subtilis) was published [2] giving a possibility for direct comparison of our model with the native structure. Our modeling appeared to be fairly successful and predicted correct protein topology and reviled the structure of regions which were not present in a crystal structure of native protein.

References: 
1. Kaminska KH, Baraniak U, Boniecki M, Nowaczyk K, Czerwoniec A, Bujnicki JM. Structural bioinformatics analysis of enzymes involved in the biosynthesis pathway of the hypermodified nucleoside ms(2)io(6)A37 in tRNA. Proteins. 2008 Jan 1;70(1):1-18. 
2. Forouhar F, Neely H, Abashidze M, Seetharaman J, Shastry R, Janjua H, Cunningham K, Ma L-C, Xiao R, Liu J, Baran MC, Acton TB, Rost B, Montelione GT, Tong L, Hunt JF. Crystal structure of tRNA isopentenylpyrophosphate transferase (BH2366) from Bacillus halodurans. To be Published. 

Download structures:
EcMiaA model
Native structure of BsMiaE - 2QGN

Read our manuscript:
Download PDF 

Gallery:

 


Comparison of structures of our model and the native structure (PDB code: 2QGN). Structures are colored according to the sequence index (N-terminus - blue, C-terminus - red). The model is of good quality in regions of catalytic core. 

Regions with corresponding secondary structure elements are colored in the same way. The structure of regions which were not present in a crystal structure are colored in a dark gray. 

Correctly predicted functionally important residues of MiaA. Amino acids predicted to bind tRNA are colored in blue, catalytic residues are colored in red, DMAPP molecule is colored in purple.