A molecular dynamics simulation of the flavin mononucleotide-RNA aptamer complex.

We report on an unrestrained molecular dynamics simulation of the flavin mononucleotide (FMN)-RNA aptamer. The simulated average structure maintains both cross-strand and intermolecular FMN-RNA nuclear Overhauser effects from the nmr experiments and has all qualitative features of the nmr structure including the G10-U12-A25 base triple and the A13-G24, A8-G28, and G9-G27 mismatches. However, the relative orientation of the hairpin loop to the remaining part of the molecule differs from the nmr structure. The simulation predicts that the flexible phosphoglycerol part of FMN moves toward G27 and forms hydrogen bonds. There are structurally long-lived water molecules in the FMN binding pocket forming hydrogen bonds within FMN and between FMN and RNA. In addition, long-lived water is found bridging primarily RNA backbone atoms. A general feature of the environment of long-lived "structural" water is at least two and in most cases three or four potential acceptor atoms. The 2'-OH group of RNA usually acts as an acceptor in interactions with the solvent. There are almost no intrastrand O2'H(n) vertical ...O4'(n + 1) hydrogen bonds within the RNA backbone. In the standard case the preferred orientation of the 2'-OH hydrogen atoms is approximately toward O3' of the same nucleotide. However, a relatively large number of conformations with the backbone torsional angle gamma in the trans orientation is found. A survey of all experimental RNA x-ray structures shows that this backbone conformation occurs but is less frequent than found in the simulation. Experimental nmr RNA aptamer structures have a higher fraction of this conformation as compared to the x-ray structures. The backbone conformation of nucleotide n + 1 with the torsional angle gamma in the trans orientation leads to a relatively short distance between 2'-OH(n) and O5'(n + 1), enabling hydrogen-bond formation. In this case the preferred orientation of the 2'-OH hydrogen atom is approximately toward O5'(n + 1). We find two relatively short and dynamically stable types of backbone-backbone next-neighbor contacts, namely C2'(H)(n) vertical ...O4'(n + 1) and C5'(H)(n + 1) vertical ...O2'(n). These interactions may affect both backbone rigidity and thermodynamic stability of RNA helical structures. Copyright 1999 John Wiley & Sons, Inc.