Prediction of RNA secondary structure based on helical regions distribution |
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Authors: | WuJu L; JiaJin W |
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Institution: | Laboratory of Bioinformation Engineering, Institute of Basic Medical Sciences, P.O. Box 130(3), Beijing 100850, China. |
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Abstract: | MOTIVATION: RNAs play an important role in many biological processes and
knowing their structure is important in understanding their function. Due
to difficulties in the experimental determination of RNA secondary
structure, the methods of theoretical prediction for known sequences are
often used. Although many different algorithms for such predictions have
been developed, this problem has not yet been solved. It is thus necessary
to develop new methods for predicting RNA secondary structure. The
most-used at present is Zuker's algorithm which can be used to determine
the minimum free energy secondary structure. However many RNA secondary
structures verified by experiments are not consistent with the minimum free
energy secondary structures. In order to solve this problem, a method used
to search a group of secondary structures whose free energy is close to the
global minimum free energy was developed by Zuker in 1989. When considering
a group of secondary structures, if there is no experimental data, we
cannot tell which one is better than the others. This case also occurs in
combinatorial and heuristic methods. These two kinds of methods have
several weaknesses. Here we show how the central limit theorem can be used
to solve these problems. RESULTS: An algorithm for predicting RNA secondary
structure based on helical regions distribution is presented, which can be
used to find the most probable secondary structure for a given RNA
sequence. It consists of three steps. First, list all possible helical
regions. Second, according to central limit theorem, estimate the
occurrence probability of every helical region based on the Monte Carlo
simulation. Third, add the helical region with the biggest probability to
the current structure and eliminate the helical regions incompatible with
the current structure. The above processes can be repeated until no more
helical regions can be added. Take the current structure as the final RNA
secondary structure. In order to demonstrate the confidence of the program,
a test on three RNA sequences: tRNAPhe, Pre-tRNATyr, and Tetrahymena
ribosomal RNA intervening sequence, is performed. AVAILABILITY: The program
is written in Turbo Pascal 7.0. The source code is available upon request.
CONTACT: Wujj@nic.bmi.ac.cn or Liwj@mail.bmi.ac.cn
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