Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz

Details Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz

2011-04-28

arxiv.org/abs/1104.5278v1

Biology

Quantitative Biology

Biomolecules

Scientific paper

Atomic-accuracy structure prediction of macromolecules is a long-sought goal of computational biophysics. Accurate modeling should be achievable by optimizing a physically realistic energy function but is presently precluded by incomplete sampling of a biopolymer's many degrees of freedom. We present herein a working hypothesis, called the "stepwise ansatz", for recursively constructing well-packed atomic-detail models in small steps, enumerating several million conformations for each monomer and covering all build-up paths. By implementing the strategy in Rosetta and making use of high-performance computing, we provide first tests of this hypothesis on a benchmark of fifteen RNA loop modeling problems drawn from riboswitches, ribozymes, and the ribosome, including ten cases that were not solvable by prior knowledge based modeling approaches. For each loop problem, this deterministic stepwise assembly (SWA) method either reaches atomic accuracy or exposes flaws in Rosetta's all-atom energy function, indicating the resolution of the conformational sampling bottleneck. To our knowledge, SWA is the first enumerative, ab initio build-up method to systematically outperform existing Monte Carlo and knowledge-based methods for 3D structure prediction. As a rigorous experimental test, we have applied SWA to a small RNA motif of previously unknown structure, the C7.2 tetraloop/tetraloop-receptor, and stringently tested this blind prediction with nucleotide-resolution structure mapping data.

Affiliated with

Also associated with

No associations

Rating

Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz does not yet have a rating. At this time, there are no reviews or comments for this scientific paper.

If you have personal experience with Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Can biopolymer structures be sampled enumeratively? Atomic-accuracy RNA loop modeling by a stepwise ansatz will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFWR-SCP-O-448826