arXiv subjects

Philippe Derreumaux

Publications and source records attributed to Philippe Derreumaux.

4 recordsLinked to original sources

arXiv2015

The coarse-grained HiRE-RNA model for de novo calculations of RNA free energy surfaces, folding pathways and complex structure prediction

HiRE-RNA is a simplified, coarse-grained RNA model for the prediction of equilibrium configurations, dynamics and thermodynamics. Using a reduced set of particles and detailed interactions accounting for base-pairing and stacking we show that non-canonical and multiple base interactions are necessary to capture the full physical behavior of complex RNAs. In this paper we give a full account of the model and we present results on the folding, stability and free energy surfaces of 16 systems with 12 to 76 nucleotides of increasingly complex architectures, ranging from monomers to dimers, using a total of 850$μ$s simulation time.

q-bio.BM↗

arXiv2014

Ab initio RNA folding

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.

q-bio.BM↗

arXiv2013

Coarse-grained simulations of RNA and DNA duplexes

Although RNAs play many cellular functions little is known about the dynamics and thermodynamics of these molecules. In principle, all-atom molecular dynamics simulations can investigate these issues, but with current computer facilities, these simulations have been limited to small RNAs and to short times. HiRe-RNA, a recently proposed high-resolution coarse-grained for RNA that captures many geometric details such as base pairing and stacking, is able to fold RNA molecules to near-native structures in a short computational time. So far it had been applied to simple hairpins, and here we present its application to duplexes of a couple dozen nucleotides and show how with our model and with Replica Exchange Molecular Dynamics (REMD) we can easily predict the correct double helix from a completely random configuration and study the dissociation curve. To show the versatility of our model, we present an application to a double stranded DNA molecule as well. A reconstruction algorithm allows us to obtain full atom structures from the coarse-grained model. Through atomistic Molecular Dynamics (MD) we can compare the dynamics starting from a representative structure of a low temperature replica or from the experimental structure, and show how the two are statistically identical, highlighting the validity of a coarse-grained approach for structured RNAs and DNAs.

q-bio.BM↗

arXiv2003

Complex folding pathways in a simple beta-hairpin

The determination of the folding mechanisms of proteins is critical to understand the topological change that can propagate Alzheimer and Creutzfeld-Jakobs diseases, among others. The computational community has paid considerable attention to this problem; however, the associated time scale, typically on the order of milliseconds or more, represents a formidable challenge. Ab initio protein folding from long molecular dynamics (MD) simulations or ensemble dynamics is not feasible with ordinary computing facilities and new techniques must be introduced. Here we present a detailed study of the folding of a 16-residue beta-hairpin, described by a generic energy model and using the activation-relaxation technique. From a total of 90 trajectories at 300 K, three folding pathways emerge. All involve a simultaneous optimization of the complete hydrophobic and hydrogen bonding interactions. The first two follow closely those observed by previous theoretical studies. The third pathway, never observed by previous all-atom folding, unfolding and equilibrium simulations, can be described as a reptation move of one strand of the beta-sheet with respect to the other. This reptation move indicates that non-native interactions can play a dominant role in the folding of secondary structures. These results point to a more complex folding picture than expected for a simple beta-hairpin.

q-bio.BM↗