The Chen Haifeng Research Group of Shanghai Jiaotong University published the latest research results on the molecular force field of nucleic acids

Recently, the internationally renowned journal International Journal of Biological Macromolecules published the latest research results
of Professor Chen Haifeng's research group of Shanghai Jiaotong University entitled "Base-Specific RNA Force Field Improving the Dynamics Conformation of Nucleotide" 。 This study proposes a base-specific RNA molecular force field (BSFF1), which effectively improves the simulation effect
against nucleic acids.
Li Zhengxin, a doctoral student at the School of Life Science and Technology of Shanghai Jiao Tong University, is the first author of the article, Mu Junxi, an undergraduate graduate of the School of Life Science and Technology, is the co-first author, and Chen Haifengjiao is the corresponding author
.

RNA, as the central link of the central law, plays a vital role in multiple physiological processes, and the new coronavirus that is currently raging is also an RNA virus
.
At present, people's research on RNA is far less mature than the study of proteins, and there are many difficulties in the traditional experimental methods in resolving RNA structure, and the number of RNA structures currently resolved (<6000) is much smaller than that of proteins (>190000).

In this context, molecular dynamics simulations that can study the structure and dynamics of biological macromolecules at the atomic level have become an important method for
studying RNA.
However, there are still major deficiencies in the force field of RNA molecules that determine their accuracy, including problems
such as over-stable base accumulation, misrepresentation of zeta/alpha dihedral angles, and easy to produce incorrect intercalation structures when simulating tetranucleotide systems.

In order to solve the above deficiencies, Chen Haifeng's team first specifically corrected the non-bond parameters that determine base accumulation through the weighting method (as shown above), and then greatly improved the simulation effect
of the tetranucleotide system by introducing lattice energy correction terms (CMAP) for zeta/alpha dilateral angles.

Simulation tests on multiple common RNA systems such as short single strands, riboswitches, double helix, spooling, k-turn, etc.
have shown that the base-specific RNA molecular force field BSFF1 can stabilize its experimental structure
.
The results of enhanced sampling showed that BSFF1 was able to fold a typical RNA hairpin from scratch and fold it sequentially from a single-stranded form to a hairpin form, which further verified the global rationality of BSFF1 and had a leading role
in studying RNA top-folding and nucleic acid molecular mechanisms.

The work was supported
by the High Performance Computing Center (HPC) of Shanghai Jiao Tong University, the National Natural Science Foundation of China (21977068 and 32171242) and the National Key Research and Development Program of China (2020YFA0907700).

Paper Link: https://doi.
org/10.
1016/j.
ijbiomac.
2022.
09.
183