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We suggest a new approach to predict the activity of DNA functional sites that is focused on the perspicuity of the prediction in terms of “a probable molecular mechanism of the site functioning”. The biological novelty of the method is in the involvement of physico-chemical and conformational DNA properties to provide clear interpretation of the obtained activity predictions in terms of a probable molecular mechanism of the site functioning. For the DNA feature analyzed, the mean value of a given DNA property averaged for a given region containing the site is calculated and studied. This approach has allowed to create a distributed and intelligent database ACTIVITY for the functional site activity prediction.