Validating accuracy of web server statistics
Proteins that interact with DNA are involved in a number of fundamental biological activities such as DNA replication, transcription, and repair (Figure 4).
A reliable identification of DNA-binding sites on DNA-binding proteins is important for functional annotation, site-directed mutagenesis, and modeling protein-DNA interactions.
Comparison of the GLP profiles of the ordered C-terminal domain of Pr P and its paralog Doppel, which is topologically identical to Pr P but does not undergo pathogenic conformational transitions, has shown that these profiles are significantly different and Doppel does not have flexible segments similar to those of Pr P (Figure 3) (Kuznetsov and Rackovsky, 2004).
We also identified a potential target for experimental structure determination aimed at obtaining a structural template that can be used to model the pathogenic conformation of prion protein (Kuznetsov and Rackovsky, 2003b).
Due to the recent technological advances in genomic data acquisition, bioinformatics has become a crucial element of genomics.
The main task of bioinformatics is to develop computational tools capable of dealing with diverse types of genomic data, filtering out noise, and finding reliable patterns associated with biological properties of interest.
Our laboratory is developing bioinformatics methods, stand-alone and web-based software for the analysis of various types of genomic data and applying these methods to genome research.
We do this by utilizing a variety of methods from statistics, information theory, classification/pattern recognition, and data mining (Figure 1). Upon changes in environment, the protein backbone can undergo significant conformational transitions (Figure 2).
) We are solving some really complex problems with web server scale, algorithms on the client side, research of different OS’s and APIs, managing multi million users products and more.One of the most striking examples of the importance of protein flexibility in the development of neurodegenerative disorders is presented by the prion protein (Pr P).The ordered C-terminal domain of this protein undergoes significant conformational changes during transition from a benign, mostly-helical protein, to a beta-sheet-rich pathogenic conformation (Prusiner, 1998).Conformationally variable positions are less conserved in evolution.
Local patterns of (a) sequence neighbors, (b) evolutionary conservation, and (c) solvent accessibility can be used to predict conformationally variable positions with balanced sensitivity and specificity, albeit with large variance at the level of individual proteins.
This finding was featured in the review article "Did the first virus self-assemble from self-replicating prion proteins and RNA?