Conformational changes in the adenine riboswitch: insights from MD simulations

The Faculty of Informatics is pleased to announce a seminar given by Francesco Di Palma

DATE: Wednesday, June 10th 2015
PLACE: USI Lugano Campus, room SI-007 Informatics building (Via G. Buffi 13)
TIME: 14.30

ABSTRACT:
Riboswitches are cis-acting genetic control elements that have been found in the untraslated region of some mRNAs in bacteria and plants. Riboswitches are known to regulate the genetic expression by means of conformational changes triggered by highly specific interactions of the aptamer with the sensed metabolite. The non-coding sequence in the mRNA of add gene from V. vulnificus contains an adenine responsive riboswitch. We first use steered MD to induce the opening of the P1 stem and investigate its stability. Our results show that the ligand directly stabilizes the P1 stem by means of stacking interactions quantitatively consistent with thermodynamic data. Then, using both umbrella sampling and a combination of metadynamics and hamiltonian replica exchange, we show that the formation of L2-L3 kissing complex cooperates with ligand binding and we quantify the ligand-induced stabilization.

Results are compatible with known experimental measurements and shed a new light on the ligand-dependent folding mechanism of the adenine riboswitch.

BIO:
Francesco Di Palma have just begun his first postdoc at Sapienza University of Rome, Italy, in the Biocomputing group headed by Anna Tramontano. He received his M.Sc. in Bioinformatics at Tor Vergata University of Rome in 2010, and his Ph.D. in Physics and Chemistry of Biological Systems under the supervision of Prof. Giovanni Bussi at SISSA, Trieste, Italy, in 2014. His research interests include the structural features and the thermodynamics of small RNA molecules and antibodies using advanced molecular dynamics techniques.

HOST: Prof. Vittorio Limongelli