| 1. |
- Ahlner, Alexandra, 1984-, et al.
(författare)
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Fractional enrichment of proteins using [2-13C]-glycerol as the carbon source facilitates measurement of excited state 13Cα chemical shifts with improved sensitivity
- 2015
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Ingår i: Journal of Biomolecular NMR. - : Springer Netherlands. - 0925-2738 .- 1573-5001. ; 62:3, s. 341-351
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Tidskriftsartikel (refereegranskat)abstract
- A selective isotope labeling scheme based on the utilization of [2-13C]-glycerol as the carbon source during protein overexpression has been evaluated for the measurement of excited state 13Cα chemical shifts using Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion (RD) experiments. As expected, the fractional incorporation of label at the Cα positions is increased two-fold relative to labeling schemes based on [2-13C]-glucose, effectively doubling the sensitivity of NMR experiments. Applications to a binding reaction involving an SH3 domain from the protein Abp1p and a peptide from the protein Ark1p establish that accurate excited state 13Cα chemical shifts can be obtained from RD experiments, with errors on the order of 0.06 ppm for exchange rates ranging from 100 to 1000 s−1, despite the small fraction of 13Cα–13Cβ spin-pairs that are present for many residue types. The labeling approach described here should thus be attractive for studies of exchanging systems using 13Cα spin probes.
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| 2. |
- Ahlner, Alexandra, et al.
(författare)
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PINT: a software for integration of peak volumes and extraction of relaxation rates
- 2013
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Ingår i: Journal of Biomolecular NMR. - : Springer Verlag (Germany). - 0925-2738 .- 1573-5001. ; 56:3, s. 191-202
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Tidskriftsartikel (refereegranskat)abstract
- We present the software Peak INTegration (PINT), designed to perform integration of peaks in NMR spectra. The program is very simple to run, yet powerful enough to handle complicated spectra. Peaks are integrated by fitting predefined line shapes to experimental data and the fitting can be customized to deal with, for instance, heavily overlapped peaks. The results can be inspected visually, which facilitates systematic optimization of the line shape fitting. Finally, integrated peak volumes can be used to extract parameters such as relaxation rates and information about low populated states. The utility of PINT is demonstrated by applications to the 59 residue SH3 domain of the yeast protein Abp1p and the 289 residue kinase domain of murine EphB2.
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| 3. |
- Bernal, D. E., et al.
(författare)
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Alternative regularizations for Outer-Approximation algorithms for convex MINLP
- 2022
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Ingår i: Journal of Global Optimization. - : Springer Nature. - 0925-5001 .- 1573-2916. ; 84:4, s. 807-842
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we extend the regularization framework from Kronqvist et al. (Math Program 180(1):285–310, 2020) by incorporating several new regularization functions and develop a regularized single-tree search method for solving convex mixed-integer nonlinear programming (MINLP) problems. We propose a set of regularization functions based on distance metrics and Lagrangean approximations, used in the projection problem for finding new integer combinations to be used within the Outer-Approximation (OA) method. The new approach, called Regularized Outer-Approximation (ROA), has been implemented as part of the open-source Mixed-integer nonlinear decomposition toolbox for Pyomo—MindtPy. We compare the OA method with seven regularization function alternatives for ROA. Moreover, we extend the LP/NLP Branch and Bound method proposed by Quesada and Grossmann (Comput Chem Eng 16(10–11):937–947, 1992) to include regularization in an algorithm denoted RLP/NLP. We provide convergence guarantees for both ROA and RLP/NLP. Finally, we perform an extensive computational experiment considering all convex MINLP problems in the benchmark library MINLPLib. The computational results show clear advantages of using regularization combined with the OA method.
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| 4. |
- Billeter, Martin, 1955
(författare)
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Non-uniform sampling in biomolecular NMR
- 2017
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Ingår i: Journal of Biomolecular Nmr. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 68:2, s. 65-66
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Björnerås, Johannes, et al.
(författare)
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Resolving complex mixtures : trilinear diffusion data
- 2014
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Ingår i: Journal of Biomolecular NMR. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 58:4, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Complex mixtures are at the heart of biology, and biomacromolecules almost always exhibit their function in a mixture, e.g., the mode of action for a spider venom is typically dependent on a cocktail of compounds, not just the protein. Information about diseases is encoded in body fluids such as urine and plasma in the form of metabolite concentrations determined by the actions of enzymes. To understand better what is happening in real living systems we urgently need better methods to characterize such mixtures. In this paper we describe a potent way to disentangle the NMR spectra of mixture components, by exploiting data that vary independently in three or more dimensions, allowing the use of powerful algorithms to decompose the data to extract the information sought. The particular focus of this paper is on NMR diffusion data, which are typically bilinear but can be extended by a third dimension to give the desired data structure.
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| 6. |
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| 7. |
- Burdakov, Oleg, et al.
(författare)
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Optimal placement of UV-based communications relay nodes
- 2010
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Ingår i: Journal of Global Optimization. - : Springer. - 0925-5001 .- 1573-2916. ; 48:4, s. 511-531
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Tidskriftsartikel (refereegranskat)abstract
- We consider a constrained optimization problem with mixed integer and real variables. It models optimal placement of communications relay nodes in the presence of obstacles. This problem is widely encountered, for instance, in robotics, where it is required to survey some target located in one point and convey the gathered information back to a base station located in another point. One or more unmanned aerial or ground vehicles (UAVs or UGVs) can be used for this purpose as communications relays. The decision variables are the number of unmanned vehicles (UVs) and the UV positions. The objective function is assumed to access the placement quality. We suggest one instance of such a function which is more suitable for accessing UAV placement. The constraints are determined by, firstly, a free line of sight requirement for every consecutive pair in the chain and, secondly, a limited communication range. Because of these requirements, our constrained optimization problem is a difficult multi-extremal problem for any fixed number of UVs. Moreover, the feasible set of real variables is typically disjoint. We present an approach that allows us to efficiently find a practically acceptable approximation to a global minimum in the problem of optimal placement of communications relay nodes. It is based on a spatial discretization with a subsequent reduction to a shortest path problem. The case of a restricted number of available UVs is also considered here. We introduce two label correcting algorithms which are able to take advantage of using some peculiarities of the resulting restricted shortest path problem. The algorithms produce a Pareto solution to the two-objective problem of minimizing the path cost and the number of hops. We justify their correctness. The presented results of numerical 3D experiments show that our algorithms are superior to the conventional Bellman-Ford algorithm tailored to solving this problem.
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| 8. |
- Carling, Kenneth, et al.
(författare)
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Confidence in heuristic solutions?
- 2015
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Ingår i: Journal of Global Optimization. - : Springer Science and Business Media LLC. - 0925-5001 .- 1573-2916. ; 63:2, s. 381-399
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Tidskriftsartikel (refereegranskat)abstract
- Solutions to combinatorial optimization problems frequently rely on heuristics to minimize an objective function. The optimum is sought iteratively and pre-setting the number of iterations dominates in operations research applications, which implies that the quality of the solution cannot be ascertained. Deterministic bounds offer a mean of ascertaining the quality, but such bounds are available for only a limited number of heuristics and the length of the interval may be difficult to control in an application. A small, almost dormant, branch of the literature suggests using statistical principles to derive statistical bounds for the optimum. We discuss alternative approaches to derive statistical bounds. We also assess their performance by testing them on 40 test p-median problems on facility location, taken from Beasley’s OR-library, for which the optimum is known. We consider three popular heuristics for solving such location problems; simulated annealing, vertex substitution, and Lagrangian relaxation where only the last offers deterministic bounds. Moreover, we illustrate statistical bounds in the location of 71 regional delivery points of the Swedish Post. We find statistical bounds reliable and much more efficient than deterministic bounds provided that the heuristic solutions are sampled close to the optimum. Statistical bounds are also found computationally affordable.
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| 9. |
- Chi N, Celestine, 1978-, et al.
(författare)
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Extending the eNOE data set of large proteins by evaluation of NOEs with unresolved diagonals.
- 2015
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Ingår i: Journal of Biomolecular NMR. - : Springer Science and Business Media LLC. - 0925-2738 .- 1573-5001. ; 62:1, s. 63-9
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Tidskriftsartikel (refereegranskat)abstract
- The representation of a protein's spatial sampling at atomic resolution is fundamental for understanding its function. NMR has been established as the best-suited technique toward this goal for small proteins. However, the accessible information content rapidly deteriorates with increasing protein size. We have recently demonstrated that for small proteins distance restraints with an accuracy smaller than 0.1 Å can be obtained by replacing traditional semi-quantitative Nuclear Overhauser Effects (NOEs) with exact NOEs (eNOE). The high quality of the data allowed us to calculate structural ensembles of the small model protein GB3 consisting of multiple rather than a single state. The analysis has been limited to small proteins because NOEs of spins with unresolved diagonal peaks cannot be used. Here we propose a simple approach to translate such NOEs into correct upper distance restraints, which opens access to larger biomolecules. We demonstrate that for 16 kDa cyclophilin A the collection of such restraints extends the original 1254 eNOEs to 3471.
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| 10. |
- Diehl, Carl, et al.
(författare)
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Conformational entropy changes upon lactose binding to the carbohydrate recognition domain of galectin-3.
- 2009
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Ingår i: Journal of Biomolecular NMR. - : Springer Science and Business Media LLC. - 1573-5001 .- 0925-2738. ; 45:1-2, s. 157-169
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Tidskriftsartikel (refereegranskat)abstract
- The conformational entropy of proteins can make significant contributions to the free energy of ligand binding. NMR spin relaxation enables site-specific investigation of conformational entropy, via order parameters that parameterize local reorientational fluctuations of rank-2 tensors. Here we have probed the conformational entropy of lactose binding to the carbohydrate recognition domain of galectin-3 (Gal3), a protein that plays an important role in cell growth, cell differentiation, cell cycle regulation, and apoptosis, making it a potential target for therapeutic intervention in inflammation and cancer. We used (15)N spin relaxation experiments and molecular dynamics simulations to monitor the backbone amides and secondary amines of the tryptophan and arginine side chains in the ligand-free and lactose-bound states of Gal3. Overall, we observe good agreement between the experimental and computed order parameters of the ligand-free and lactose-bound states. Thus, the (15)N spin relaxation data indicate that the molecular dynamics simulations provide reliable information on the conformational entropy of the binding process. The molecular dynamics simulations reveal a correlation between the simulated order parameters and residue-specific backbone entropy, re-emphasizing that order parameters provide useful estimates of local conformational entropy. The present results show that the protein backbone exhibits an increase in conformational entropy upon binding lactose, without any accompanying structural changes.
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