Limits in accuracy and a strategy of RNA structure prediction using experimental information

• Published in: Nucleic acids research Vol. 47; no. 11; pp. 5563 - 5572
• Main Authors: Wang, Jian, Williams, Benfeard, Chirasani, Venkata R, Krokhotin, Andrey, Das, Rajeshree, Dokholyan, Nikolay V
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 20-06-2019
• Subjects: Algorithms; Base Sequence; Computational Biology; Computational Biology - methods; Computer Simulation; Models, Molecular; Nucleic Acid Conformation; RNA - chemistry; RNA Folding; RNA, Catalytic - chemistry; Thermodynamics
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkz427

RNA structural complexity and flexibility present a challenge for computational modeling efforts. Experimental information and bioinformatics data can be used as restraints to improve the accuracy of RNA tertiary structure prediction. Regarding utilization of restraints, the fundamental questions are: (i) What is the limit in prediction accuracy that one can achieve with arbitrary number of restraints? (ii) Is there a strategy for selection of the minimal number of restraints that would result in the best structural model? We address the first question by testing the limits in prediction accuracy using native contacts as restraints. To address the second question, we develop an algorithm based on the distance variation allowed by secondary structure (DVASS), which ranks restraints according to their importance to RNA tertiary structure prediction. We find that due to kinetic traps, the greatest improvement in the structure prediction accuracy is achieved when we utilize only 40-60% of the total number of native contacts as restraints. When the restraints are sorted by DVASS algorithm, using only the first 20% ranked restraints can greatly improve the prediction accuracy. Our findings suggest that only a limited number of strategically selected distance restraints can significantly assist in RNA structure modeling.