Efficient sampling of protein structures by model hopping.
Ontology highlight
ABSTRACT:
SUBMITTER: Kwak W
PROVIDER: S-EPMC1356668 | biostudies-literature | 2005 Sep
REPOSITORIES: biostudies-literature
Publications
Efficient sampling of protein structures by model hopping.
Kwak Wooseop W Hansmann Ulrich H E UH
Physical review letters 20050922 13
We introduce a novel simulation method, model hopping, that enhances sampling of low-energy configurations in complex systems. The approach is illustrated for a protein-folding problem. Thermodynamic quantities of proteins with up to 46 residues are evaluated from all-atom simulations with this method. ...[more]
Similar Datasets
Project description:Clearly, a protein cannot sample all of its conformations (e.g., approximately 3(100) approximately 10(48) for a 100 residue protein) on an in vivo folding timescale (<1 s). To investigate how the conformational dynamics of a protein can accommodate subsecond folding time scales, we introduce the concept of the native topomer, which is the set of all structures similar to the native structure (obtainable from the native structure through local backbone coordinate transformations that do not disrupt the covalent bonding of the peptide backbone). We have developed a computational procedure for estimating the number of distinct topomers required to span all conformations (compact and semicompact) for a polypeptide of a given length. For 100 residues, we find approximately 3 x 10(7) distinct topomers. Based on the distance calculated between different topomers, we estimate that a 100-residue polypeptide diffusively samples one topomer every approximately 3 ns. Hence, a 100-residue protein can find its native topomer by random sampling in just approximately 100 ms. These results suggest that subsecond folding of modest-sized, single-domain proteins can be accomplished by a two-stage process of (i) topomer diffusion: random, diffusive sampling of the 3 x 10(7) distinct topomers to find the native topomer ( approximately 0.1 s), followed by (ii) intratopomer ordering: nonrandom, local conformational rearrangements within the native topomer to settle into the precise native state.
| S-EPMC15813 | biostudies-literature
Project description:We have investigated photoinduced hole hopping in a Pseudomonas aeruginosa azurin mutant Re126WWCuI, where two adjacent tryptophan residues (W124 and W122) are inserted between the CuI center and a Re photosensitizer coordinated to a H126 imidazole (Re = ReI(H126)(CO)3(dmp)+, dmp = 4,7-dimethyl-1,10-phenanthroline). Optical excitation of this mutant in aqueous media (?40 ?M) triggers 70 ns electron transport over 23 Å, yielding a long-lived (120 ?s) ReI(H126)(CO)3(dmp•-)WWCuII product. The Re126FWCuI mutant (F124, W122) is not redox-active under these conditions. Upon increasing the concentration to 0.2-2 mM, {Re126WWCuI}2 and {Re126FWCuI}2 are formed with the dmp ligand of the Re photooxidant of one molecule in close contact (3.8 Å) with the W122' indole on the neighboring chain. In addition, {Re126WWCuI}2 contains an interfacial tryptophan quadruplex of four indoles (3.3-3.7 Å apart). In both mutants, dimerization opens an intermolecular W122' ? //*Re ET channel (// denotes the protein interface, *Re is the optically excited sensitizer). Excited-state relaxation and ET occur together in two steps (time constants of ?600 ps and ?8 ns) that lead to a charge-separated state containing a Re(H126)(CO)3(dmp•-)//(W122•+)' unit; then (CuI)' is oxidized intramolecularly (60-90 ns) by (W122•+)', forming ReI(H126)(CO)3(dmp•-)WWCuI//(CuII)'. The photocycle is closed by ?1.6 ?s ReI(H126)(CO)3(dmp•-) ? //(CuII)' back ET that occurs over 12 Å, in contrast to the 23 Å, 120 ?s step in Re126WWCuI. Importantly, dimerization makes Re126FWCuI photoreactive and, as in the case of {Re126WWCuI}2, channels the photoproduced "hole" to the molecule that was not initially photoexcited, thereby shortening the lifetime of ReI(H126)(CO)3(dmp•-)//CuII. Although two adjacent W124 and W122 indoles dramatically enhance CuI ? *Re intramolecular multistep ET, the tryptophan quadruplex in {Re126WWCuI}2 does not accelerate intermolecular electron transport; instead, it acts as a hole storage and crossover unit between inter- and intramolecular ET pathways. Irradiation of {Re126WWCuII}2 or {Re126FWCuII}2 also triggers intermolecular W122' ? //*Re ET, and the Re(H126)(CO)3(dmp•-)//(W122•+)' charge-separated state decays to the ground state by ?50 ns ReI(H126)(CO)3(dmp•-)+ ? //(W122•+)' intermolecular charge recombination. Our findings shed light on the factors that control interfacial hole/electron hopping in protein complexes and on the role of aromatic amino acids in accelerating long-range electron transport.
| S-EPMC6384139 | biostudies-literature
Project description:Associative memory Hamiltonian structure prediction potentials are not overly rugged, thereby suggesting their landscapes are like those of actual proteins. In the present contribution we show how basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes. For small systems the basin-hopping algorithm succeeds in locating both lower minima and conformations closer to the experimental structure than does molecular dynamics with simulated annealing. For large systems the efficiency of basin-hopping decreases for our initial implementation, where the steps consist of random perturbations to the Cartesian coordinates. We implemented umbrella sampling using basin-hopping to further confirm when the global minima are reached. We have also improved the energy surface by employing bioinformatic techniques for reducing the roughness or variance of the energy surface. Finally, the basin-hopping calculations have guided improvements in the excluded volume of the Hamiltonian, producing better structures. These results suggest a novel and transferable optimization scheme for future energy function development.
| S-EPMC2674628 | biostudies-literature
Project description:A new and efficient Monte Carlo algorithm for sampling protein configurations in the continuous space is presented; the efficiency of this algorithm, named Local Moves for Proteins (LMProt), was compared to other alternative algorithms. For this purpose, we used an intrachain interaction energy function that is proportional to the root mean square deviation (rmsd) with respect to alpha-carbons from native structures of real proteins. For phantom chains, the LMProt method is approximately 10(4) and 20 times faster than the algorithms Thrashing (no local moves) and Sevenfold Way (local moves), respectively. Additionally, the LMProt was tested for real chains (excluded-volume all-atoms model); proteins 5NLL (138 residues) and 1BFF (129 residues) were used to determine the folding success xi as a function of the number eta of residues involved in the chain movements, and as a function of the maximum amplitude of atomic displacement delta r(max). Our results indicate that multiple local moves associated with relative chain flexibility, controlled by appropriate adjustments for eta and delta r(max), are essential for configurational search efficiency.
| S-EPMC1304563 | biostudies-literature
Project description:Human decisions are based on finite information, which makes them inherently imprecise. But what determines the degree of such imprecision? Here, we develop an efficient coding framework for higher-level cognitive processes in which information is represented by a finite number of discrete samples. We characterize the sampling process that maximizes perceptual accuracy or fitness under the often-adopted assumption that full adaptation to an environmental distribution is possible, and show how the optimal process differs when detailed information about the current contextual distribution is costly. We tested this theory on a numerosity discrimination task, and found that humans efficiently adapt to contextual distributions, but in the way predicted by the model in which people must economize on environmental information. Thus, understanding decision behavior requires that we account for biological restrictions on information coding, challenging the often-adopted assumption of precise prior knowledge in higher-level decision systems.
| S-EPMC7492090 | biostudies-literature
Project description:RNA-protein complexes underlie numerous cellular processes including translation, splicing, and posttranscriptional regulation of gene expression. The structures of these complexes are crucial to their functions but often elude high-resolution structure determination. Computational methods are needed that can integrate low-resolution data for RNA-protein complexes while modeling de novo the large conformational changes of RNA components upon complex formation. To address this challenge, we describe RNP-denovo, a Rosetta method to simultaneously fold-and-dock RNA to a protein surface. On a benchmark set of diverse RNA-protein complexes not solvable with prior strategies, RNP-denovo consistently sampled native-like structures with better than nucleotide resolution. We revisited three past blind modeling challenges involving the spliceosome, telomerase, and a methyltransferase-ribosomal RNA complex in which previous methods gave poor results. When coupled with the same sparse FRET, crosslinking, and functional data used previously, RNP-denovo gave models with significantly improved accuracy. These results open a route to modeling global folds of RNA-protein complexes from low-resolution data.
| S-EPMC6318048 | biostudies-literature
Project description:Scientific advance is often driven by identifying conceptually simple models underlying complex phenomena. This process commonly ignores imperfections which, however, might give rise to non-trivial collective behavior. For example, already a small amount of disorder can dramatically change the transport properties of a system compared to the underlying simple model. While systems with disordered potentials were already studied in detail, experimental investigations on systems with disordered hopping are still in its infancy. To this end, we experimentally study a dipole-dipole-interacting three-dimensional Rydberg system and map it onto a simple XY model with random couplings by spectroscopic evidence. We discuss the localization-delocalization crossover emerging in the model and present experimental signatures of it. Our results demonstrate that Rydberg systems are a useful platform to study random hopping models with the ability to access the microscopic degrees of freedom. This will allow to study transport processes and localization phenomena in random hopping models with a high level of control.
| S-EPMC8632899 | biostudies-literature
Project description:High-resolution structure determination of small proteins in solution is one of the big assets of NMR spectroscopy in structural biology. Improvements in the efficiency of NMR structure determination by advances in NMR experiments and automation of data handling therefore attracts continued interest. Here, non-uniform sampling (NUS) of 3D heteronuclear-resolved [(1)H,(1)H]-NOESY data yielded two- to three-fold savings of instrument time for structure determinations of soluble proteins. With the 152-residue protein NP_372339.1 from Staphylococcus aureus and the 71-residue protein NP_346341.1 from Streptococcus pneumonia we show that high-quality structures can be obtained with NUS NMR data, which are equally well amenable to robust automated analysis as the corresponding uniformly sampled data.
| S-EPMC4576834 | biostudies-literature
Project description:PURPOSE:To develop and evaluate a novel deep learning-based image reconstruction approach called MANTIS (Model-Augmented Neural neTwork with Incoherent k-space Sampling) for efficient MR parameter mapping. METHODS:MANTIS combines end-to-end convolutional neural network (CNN) mapping, incoherent k-space undersampling, and a physical model as a synergistic framework. The CNN mapping directly converts a series of undersampled images straight into MR parameter maps using supervised training. Signal model fidelity is enforced by adding a pathway between the undersampled k-space and estimated parameter maps to ensure that the parameter maps produced synthesized k-space consistent with the acquired undersampling measurements. The MANTIS framework was evaluated on the T2 mapping of the knee at different acceleration rates and was compared with 2 other CNN mapping methods and conventional sparsity-based iterative reconstruction approaches. Global quantitative assessment and regional T2 analysis for the cartilage and meniscus were performed to demonstrate the reconstruction performance of MANTIS. RESULTS:MANTIS achieved high-quality T2 mapping at both moderate (R = 5) and high (R = 8) acceleration rates. Compared to conventional reconstruction approaches that exploited image sparsity, MANTIS yielded lower errors (normalized root mean square error of 6.1% for R = 5 and 7.1% for R = 8) and higher similarity (structural similarity index of 86.2% at R = 5 and 82.1% at R = 8) to the reference in the T2 estimation. MANTIS also achieved superior performance compared to direct CNN mapping and a 2-step CNN method. CONCLUSION:The MANTIS framework, with a combination of end-to-end CNN mapping, signal model-augmented data consistency, and incoherent k-space sampling, is a promising approach for efficient and robust estimation of quantitative MR parameters.
| S-EPMC7144418 | biostudies-literature
Project description:Case-cohort (Prentice, 1986) and nested case-control (Thomas, 1977) designs have been widely used as a cost-effective alternative to the full-cohort design. In this article, we propose an efficient likelihood-based estimation method for the accelerated failure time model under case-cohort and nested case-control designs. An EM algorithm is developed to maximize the likelihood function and a kernel smoothing technique is adopted to facilitate the estimation in the M-step of the EM algorithm. We show that the proposed estimators for the regression coefficients are consistent and asymptotically normal. The asymptotic variance of the estimators can be consistently estimated using an EM-aided numerical differentiation method. Simulation studies are conducted to evaluate the finite-sample performance of the estimators and an application to a Wilms tumor data set is also given to illustrate the methodology.
| S-EPMC5288392 | biostudies-literature