| 1. |
- Cruz, Jose Almeida, et al.
(författare)
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RNA-Puzzles : A CASP-like evaluation of RNA three-dimensional structure prediction
- 2012
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Ingår i: RNA. - : Cold Spring Harbor Laboratory. - 1355-8382 .- 1469-9001. ; 18:4, s. 610-625
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of a first, collective, blind experiment in RNA three-dimensional (3D) structure prediction, encompassing three prediction puzzles. The goals are to assess the leading edge of RNA structure prediction techniques; compare existing methods and tools; and evaluate their relative strengths, weaknesses, and limitations in terms of sequence length and structural complexity. The results should give potential users insight into the suitability of available methods for different applications and facilitate efforts in the RNA structure prediction community in ongoing efforts to improve prediction tools. We also report the creation of an automated evaluation pipeline to facilitate the analysis of future RNA structure prediction exercises.
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| 2. |
- Dourado, Daniel F. A. R., et al.
(författare)
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A multiscale approach to predicting affinity changes in protein-protein interfaces
- 2014
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Ingår i: Proteins. - : Wiley. - 0887-3585 .- 1097-0134. ; 82:10, s. 2681-2690
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Tidskriftsartikel (refereegranskat)abstract
- Substitution mutations in protein-protein interfaces can have a substantial effect on binding, which has consequences in basic and applied biomedical research. Experimental expression, purification, and affinity determination of protein complexes is an expensive and time-consuming means of evaluating the effect of mutations, making a fast and accurate in silico method highly desirable. When the structure of the wild-type complex is known, it is possible to economically evaluate the effect of point mutations with knowledge based potentials, which do not model backbone flexibility, but these have been validated only for single mutants. Substitution mutations tend to induce local conformational rearrangements only. Accordingly, ZEMu (Zone Equilibration of Mutants) flexibilizes only a small region around the site of mutation, then computes its dynamics under a physics-based force field. We validate with 1254 experimental mutants (with 1-15 simultaneous substitutions) in a wide variety of different protein environments (65 protein complexes), and obtain a significant improvement in the accuracy of predicted Delta Delta G.
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| 3. |
- Flores, Samuel Coulbourn
(författare)
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Fast fitting to low resolution density maps : elucidating large-scale motions of the ribosome
- 2014
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 42:2, s. e9-
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Tidskriftsartikel (refereegranskat)abstract
- Determining the conformational rearrangements of large macromolecules is challenging experimentally and computationally. Case in point is the ribosome; it has been observed by high-resolution crystallography in several states, but many others are known only from low-resolution methods including cryoelectron microscopy. Combining these data into dynamical trajectories that may aid understanding of its largest-scale conformational changes has so far remained out of reach of computational methods. Most existing methods either model all atoms explicitly, resulting in often prohibitive cost, or use approximations that lose interesting structural and dynamical detail. In this work, I introduce Internal Coordinate Flexible Fitting, which uses full atomic forces and flexibility in limited regions of a model, capturing extensive conformational rearrangements at low cost. I use it to turn multiple low-resolution density maps, crystallographic structures and biochemical information into unified all-atoms trajectories of ribosomal translocation. Internal Coordinate Flexible Fitting is three orders of magnitude faster than the most comparable existing method.
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| 4. |
- Flores, Samuel Coulbourn, et al.
(författare)
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Fast Flexible Modeling of RNA Structure Using Internal Coordinates
- 2011
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Ingår i: IEEE/ACM Transactions on Computational Biology & Bioinformatics. - 1545-5963 .- 1557-9964. ; 8:5, s. 1247-1257
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Tidskriftsartikel (refereegranskat)abstract
- Modeling the structure and dynamics of large macromolecules remains a critical challenge. Molecular dynamics (MD) simulations are expensive because they model every atom independently, and are difficult to combine with experimentally derived knowledge. Assembly of molecules using fragments from libraries relies on the database of known structures and thus may not work for novel motifs. Coarse-grained modeling methods have yielded good results on large molecules but can suffer from difficulties in creating more detailed full atomic realizations. There is therefore a need for molecular modeling algorithms that remain chemically accurate and economical for large molecules, do not rely on fragment libraries, and can incorporate experimental information. RNABuilder works in the internal coordinate space of dihedral angles and thus has time requirements proportional to the number of moving parts rather than the number of atoms. It provides accurate physics-based response to applied forces, but also allows user-specified forces for incorporating experimental information. A particular strength of RNABuilder is that all Leontis-Westhof basepairs can be specified as primitives by the user to be satisfied during model construction. We apply RNABuilder to predict the structure of an RNA molecule with 160 bases from its secondary structure, as well as experimental information. Our model matches the known structure to 10.2 Angstroms RMSD and has low computational expense.
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