The experimental analysis of protein and RNA structure is far from meeting the demand, so computational prediction becomes necessary. Protein structure prediction is difficult, RNA structure prediction is more difficult, and the high-precision correction of the predicted structure model is even more difficult. With Dr. Xiong Peng as the first author, Dr. Zhan Jian and I as the corresponding authors, and Professor Wu Ruibo of Sun Yat sen University, the Briq RNA method can effectively improve the initial RNA structure model which is close to the natural structure, so as to achieve the goal of high-precision RNA structure prediction. The realization of high-precision RNA structure prediction will have a profound impact on the discovery and interpretation of non coding RNA function and the design and development of RNA drugs. This work is published in nature communications 12, article number: 2777 (2021).

The research on proteins has been one of the focuses of biologists for a long time. Proteins seem to control all aspects from catalytic chemical reaction, molecular transportation, structural support, immunity to the regulation of life process. However, it is strange that only 1.5% of human genome is used to encode proteins, and more than 70% of human genome is transcribed into non coding RNA. More and more evidence shows that these hidden behind the scenes, with at least ten times the amount of protein, play many unknown important roles, and the tip of the iceberg is just emerging.

But RNA is more difficult to study than protein. First of all, it is chemically unstable and easy to degrade. More importantly, its structure is also unstable. Only a few RNA can form stable static structure, which can be analyzed by X-ray crystal diffraction, nuclear magnetic resonance and freeze electron microscopy. So far, only 3% of the structures in PDB structure database contain RNA. Without structure as a clue, it is difficult to study its function, let alone its mechanism.

Because physical methods are difficult to analyze the structure of most RNA, it has become a common tool for molecular biologists to predict the structure by calculation, although the accuracy is still not so reliable. According to RNA puzzles (RNA structure competition similar to protein structure prediction CASP competition), if a homologous RNA with structure can be found, the more reliable tool at present is homologous modeling. Small RNAs with simple structure can sometimes be predicted better, but these RNA models must be refined at the atomic level, Because ab initio prediction often starts from simplified models, and homologous models often have missing regions. However, at present, there are few methods for high-precision modification of RNA structure model, and they can only be adjusted in a very small range near the original model structure, because the structure is easy to become worse rather than better. In fact, even the high-precision modification of protein structure which has been developed for decades has not been a good way. Whether it is protein or RNA, the fundamental reason why structural optimization is so difficult is that there is no high-precision energy function at the atomic level.

Briq RNA, with Dr. Xiong Peng as the first author, Dr. Zhan Jian and I as the corresponding authors, started cooperation with Professor Wu Ruibo of Sun Yat sen University at Griffith University in Australia, and completed a method of high-precision RNA structure correction in the later stage of Shenzhen Bay laboratory. This method designs a new statistical Briq energy function, which is completely different from that used in protein and RNA today, because the key factor of protein structural stability is the hydrophobicity with little directivity, the conformation of protein polypeptide main chain determines the direction of branch chain, and the key factor of RNA structural stability is the stacking of base pairs with great directivity, The alignment of phosphate ribose backbone is determined by base pairing. Therefore, the Briq energy function designs a statistical potential with six dimensional space to describe the directional base base, base oxygen atom, oxygen atom oxygen atom interactions, supplemented by the rotational isomers of the main chain. At the same time, in order to reduce the indirect interactions in the data statistics, the Briq energy function corrects the base base interaction according to the quantum calculation results, Finally, the Briq RNA method uses the base centered folding tree sampling algorithm to improve the atomic accuracy of RNA three-dimensional structure model. Although the degree of improvement is high or low for different RNA, all the initial models which are close to the natural structure, no matter what method is used to predict, can be improved. Thus, an important step in the correct direction is taken in the high-precision correction of RNA structure! This work will have a great impact on the development of RNA energy function, high-precision prediction of RNA structure, prediction and mechanism of RNA function, and drug development in the future.

Through the combination of calculation and experiment, our group is engaged in the basic research on the relationship between protein / RNA sequence, structure and function, and the applied research on biomolecular detection and drug development. Looking for postdoctoral, research assistant and assistant researcher with computing and experimental experience in RNA.