Parallel Folding Research Articles

Melamine formaldehyde resin adhesive toughened with graphene oxide: Structures and properties

The melamine-formaldehyde (MF) resin adhesive was modified by graphene oxide (GO), the chemical structure, wettability, bonding performance, tensile properties, curing performance and thermal properties of the modified resin were analyzed, and the toughening mechanism was also discussed in this study. The results showed that: (1) The MF resin with a high molar ratio possessed stable methylene ether bonds, which could easily generate parallel folding in space to form a π-π stacking supramolecular self-assembly special structure, with the potential of enhancing the toughness of molecular structures. (2) GO contained a large number of oxygen-containing reactive functional groups, which could further lower the curing temperature of the MF resin. A dense cross-linked network structure improved the thermal stability of the resin. (3) The bonding strength and toughness of the resin were significantly improved when the content of GO was 0.1 wt%. However, due to the large specific surface area and the intense π-π interaction between sheets, GO was easy to agglomerate, and the properties of the resin with GO content of 0.4 wt% degraded sharply. (4) The crystallinity of the MF resin modified by GO decreased, and the surface energy and plastic deformation energy increased due to the increased fracture crack path and fracture surface of the resin, which was the macro-reason for the improvement of toughness. (5) The strong π-π interaction between GO sheets and π-π accumulation between triazine rings were like parallel “springs” in the molecular structure of the resin, which might be the internal reason for the improvement of toughness. In addition, it was also proved that this special structure could limit the activity of hydroxymethyl and the release of free formaldehyde in the resin.

Adaptive patch grid strategy for parallel protein folding using atomic burials with NAMD

The definition of protein structures is an important research topic in molecular biology currently, since there is a direct relationship between the function of the protein in the organism and the 3D geometric configuration it adopts. The transformations that occur in the protein structure from the 1D configuration to the 3D form are called protein folding. Ab initio protein folding methods use physical forces to model the interactions among the atoms that compose the protein. In order to accelerate those methods, parallel tools such as NAMD were proposed. In this paper, we propose two contributions for parallel protein folding simulations: (a) adaptive patch grid (APG) and (b) the addition of atomic burials (AB) to the traditional forces used in the simulation. With APG, we are able to adapt the simulation box (patch grid) to the current shape of the protein during the folding process. AB forces relate the 3D protein structure to its geometric center and are adequate for modeling globular proteins. Thus, adding AB to the forces used in parallel protein folding potentially increases the quality of the result for this class of proteins. APG and AB were implemented in NAMD and tested in supercomputer environments. Our results show that, with APG, we are able to reduce the execution time of the folding simulation of protein 4LNZ (5,714 atoms, 15 million time steps) from 12 hours and 36 minutes to 11 hours and 8 minutes, using 16 nodes (256 CPU cores). We also show that our APG+AB strategy was successfully used in a realistic protein folding simulation (1.7 billion time steps).

Experimental study on fatigue behavior of trapezoidal corrugated-web girders based on T-section members

Fatigue of steel corrugated-web girders (CWGs) is a new research topic. This study uses trapezoidal corrugated-web T-section members (CWTs) to lower the cost of fatigue tests when investigating the fatigue behavior of a trapezoidal CWG. First, static tests were conducted, and the CWG under a bending moment and CWT under an axial force were compared, which verified that the flanges had the same stress distribution characteristics under equivalent loads. This demonstrates that it is suitable to investigate the fatigue behavior of a CWG using a CWT. Second, fatigue tests were performed on trapezoidal CWT specimens with two different waveform radii, R30 and R60, and their hot spot stress concentration factors at the fatigue critical location of CWG (the intersection between a parallel fold and an inclined fold of a web) were obtained, which reached 1.63 and 1.54, respectively. Of the 18 CWT specimens that experienced fatigue failure, 72 % of the initial cracks occurred at point S, indicating that this location was the most susceptible to fatigue cracking. The same S-N curve (log10N = 12.928-3log10Δσhs) could be applied in calculating the fatigue strengths of CWTs with different wave radii (R30 and R60) when the hot spot stress range that considered the stress concentration factor (SCF) was used.

Top-Down Machine Learning of Coarse-Grained Protein Force Fields.

Developing accurate and efficient coarse-grained representations of proteins is crucial for understanding their folding, function, and interactions over extended time scales. Our methodology involves simulating proteins with molecular dynamics and utilizing the resulting trajectories to train a neural network potential through differentiable trajectory reweighting. Remarkably, this method requires only the native conformation of proteins, eliminating the need for labeled data derived from extensive simulations or memory-intensive end-to-end differentiable simulations. Once trained, the model can be employed to run parallel molecular dynamics simulations and sample folding events for proteins both within and beyond the training distribution, showcasing its extrapolation capabilities. By applying Markov state models, native-like conformations of the simulated proteins can be predicted from the coarse-grained simulations. Owing to its theoretical transferability and ability to use solely experimental static structures as training data, we anticipate that this approach will prove advantageous for developing new protein force fields and further advancing the study of protein dynamics, folding, and interactions.

Unveiling Metastable Ensembles of GRB2 and the Relevance of Interdomain Communication during Folding.

The folding process of multidomain proteins is a highly intricate phenomenon involving the assembly of distinct domains into a functional three-dimensional structure. During this process, each domain may fold independently while interacting with others. The folding of multidomain proteins can be influenced by various factors, including their composition, the structure of each domain, or the presence of disordered regions, as well as the surrounding environment. Misfolding of multidomain proteins can lead to the formation of nonfunctional structures associated with a range of diseases, including cancers or neurodegenerative disorders. Understanding this process is an important step for many biophysical analyses such as stability, interaction, malfunctioning, and rational drug design. One such multidomain protein is growth factor receptor-bound protein 2 (GRB2), an adaptor protein that is essential in regulating cell survival. GRB2 consists of one central Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. The SH2 domain interacts with phosphotyrosine regions in other proteins, while the SH3 domains recognize proline-rich regions on protein partners during cell signaling. Here, we combined computational and experimental techniques to investigate the folding process of GRB2. Through computational simulations, we sampled the conformational space and mapped the mechanisms involved by the free energy profiles, which may indicate possible intermediate states. From the molecular dynamics trajectories, we used the energy landscape visualization method (ELViM), which allowed us to visualize a three-dimensional (3D) representation of the overall energy surface. We identified two possible parallel folding routes that cannot be seen in a one-dimensional analysis, with one occurring more frequently during folding. Supporting these results, we used differential scanning calorimetry (DSC) and fluorescence spectroscopy techniques to confirm these intermediate states in vitro. Finally, we analyzed the deletion of domains to compare our model outputs to previously published results, supporting the presence of interdomain modulation. Overall, our study highlights the significance of interdomain communication within the GRB2 protein and its impact on the formation, stability, and structural plasticity of the protein, which are crucial for its interaction with other proteins in key signaling pathways.

Numerical and theoretical analysis of normal stress distribution in flanges of I-girders with trapezoidal corrugated webs under uniform bending

I-girders with corrugated webs (IGCWs) are a new type of structure that has been increasingly used in engineering. The normal stress distribution in flanges of IGCWs is quite complicated compared with that of conventional I-girders under in-plane loads. This study numerically and theoretically investigates the normal stress distribution rules and mechanisms in flanges of I-girders with trapezoidal corrugated webs (IGTCWs) under uniform bending in the elastic stage. First, finite element (FE) modelling was developed using ABAQUS software and verified by the available experimental results. Based on the verified FE models, a detailed analysis of the normal stress distribution in flanges of IGTCWs was performed. The results show that the normal stresses are nearly uniformly distributed over the flange in cross-sections with inclined web folds. Normal stresses in cross-sections with parallel web folds are approximately linearly distributed along the flange width, with stresses away from the corrugated web side being much larger than those near it. Its mechanism is explored using a secondary transverse moment theory, which is improved and completed by considering the proposed effective cross-section coefficient and equivalent width coefficient for the action of shear flow. The reliability of this theory was verified through comparison with the normal stress difference and distribution results of the supplementary FE models. Finally, the formulae for calculating the normal stresses in flanges of different cross-sections of IGTCWs under uniform bending are presented. These formulae suggest that secondary normal stresses generated by secondary transverse moments in cross-sections with parallel web folds account for 7% to 13% of the total normal stresses and cannot be ignored in the stress analysis.

Excited-State Charge Transfer, Proton Transfer, and Exciplex Formation Revealed by Ultrafast Time-Resolved Spectroscopy in Human Telomeric Ribonucleic Acid Quadruplex.

Guanine quadruplexes (GQs), important for genome stability and biotechnology application, can form from both DNA and RNA. However, unlike the study of DNA GQs, little research has been conducted on excited states of GQs from RNA, which due to the ribose 2'-hydroxy group have structures distinct from their DNA counterparts. Combining ultrafast broadband time-resolved fluorescence and transient absorption measurements, we report the first direct probe of excitation dynamics for a bimolecular GQ from human telomeric repeat-containing RNA taking the typical highly compacted parallel folding with a propeller-like loop structure. The result revealed a multichannel decay containing an unusual high-energy excimer featuring charge transfer deactivated by rapid proton transfer in the tetrad core region. It also identified an unprecedented exciplex displaying massively red-shifted fluorescence produced from charge transfer in the loop region. The findings underscore the role of structural conformation and base content in determining the energy, electronic attribution, and decay dynamics of GQ excited states.

Automated identification and mapping of geological folds in cross sections

Abstract Cross sections carry information on the spatial distribution of rock strata and the development of geological structures, and it is an important data source for three-dimensional (3D) geological modeling. However, the interpretation and mapping of geological structures in sections by means of manual interpretation are inefficient and costly, and the performance varies greatly with the experts’ ability and experience. The objective of this article is to develop an automatic recognition and mapping method for folds in cross sections. This method mainly includes identifying folds based on stratigraphic sequence characteristics (symmetrical and repetitive), classifying fold types based on geometric attributes of folds (interval scheduling, strike, and section morphology), optimizing strata based on the superposition principle and area conservation principle, and constructing the polygon features of folds. Based on experiments in the Parallel Fold Belt of Eastern Sichuan and the central Appalachian fold-thrust belt in the Appalachian Mountains, the method presented in this article can effectively be used for automatic recognition and high-quality mapping of folds in the cross sections. The method provides a good source of geological cross-sectional data for the 3D modeling of geologic bodies.

Trioxacarcin A Interactions with G-Quadruplex DNA Reveal Its Potential New Targets as an Anticancer Agent.

Trioxacarcin (TXN) A was reported to be an anticancer agent through alkylation of dsDNA. G-quadruplex DNA (G4-DNA) is frequently formed in the promoter regions of oncogenes and the ends of telomerase genes, considered as promising drug targets for anticancer therapy. There are no reports about TXN A interactions with G4-DNA. Here, we tested TXN A's interactions with several G4-DNA oligos with parallel, antiparallel, or hybrid folding, respectively. We demonstrated that TXN A preferred to alkylate one flexible guanine in the loops of parallel G4-DNA. The position of the alkylated guanine is in favor of interactions of G4-DNA with TXN A. The structure of TXN A covalently bound RET G4-DNA indicated that TXN A alkylation on RET G4-DNA stabilizes the G4-DNA conformation. These studies opened a new window of how TXN A interacted with G4-DNA, which might hint a new mode of its function as an anticancer agent.

Meisosomes, folded membrane microdomains between the apical extracellular matrix and epidermis.

Apical extracellular matrices (aECMs) form a physical barrier to the environment. In Caenorhabditis elegans, the epidermal aECM, the cuticle, is composed mainly of different types of collagen, associated in circumferential ridges separated by furrows. Here, we show that in mutants lacking furrows, the normal intimate connection between the epidermis and the cuticle is lost, specifically at the lateral epidermis, where, in contrast to the dorsal and ventral epidermis, there are no hemidesmosomes. At the ultrastructural level, there is a profound alteration of structures that we term 'meisosomes,' in reference to eisosomes in yeast. We show that meisosomes are composed of stacked parallel folds of the epidermal plasma membrane, alternately filled with cuticle. We propose that just as hemidesmosomes connect the dorsal and ventral epidermis, above the muscles, to the cuticle, meisosomes connect the lateral epidermis to it. Moreover, furrow mutants present marked modifications of the biomechanical properties of their skin and exhibit a constitutive damage response in the epidermis. As meisosomes co-localise to macrodomains enriched in phosphatidylinositol (4,5) bisphosphate, they could conceivably act, like eisosomes, as signalling platforms, to relay tensile information from the aECM to the underlying epidermis, as part of an integrated stress response to damage.

Transmembrane capability of DNA origami sheet enhanced by 3D configurational changes

DNA origami-engineered nanostructures are widely used in biomedical applications involving transmembrane delivery. Here, we propose a method to enhance the transmembrane capability of DNA origami sheets by changing their configuration from two-dimensional to three-dimensional. Three DNA nanostructures are designed and constructed, including the two-dimensional rectangular DNA origami sheet, the DNA tube, and the DNA tetrahedron. The latter two are the variants of the DNA origami sheet with three-dimensional morphologies achieved through one-step folding and multi-step parallel folding separately. The design feasibility and structural stability of three DNA nanostructures are confirmed by molecular dynamics simulations. The fluorescence signals of the brain tumor models demonstrate that the tubular and the tetrahedral configurational changes could dramatically increase the penetration efficiency of the original DNA origami sheet by about three and five times, respectively. Our findings provide constructive insights for further rational designs of DNA nanostructures for transmembrane delivery.

Formation and modification of wrinkle ridges in the central Tharsis region of Mars as constrained by detailed geomorphological mapping and landsystem analysis

Wrinkle ridges are common landforms documented on all rocky planets and the Moon in the inner solar system. Despite the long research history, their formation mechanisms remain debated. A key unresolved issue is whether the wrinkle-ridge formation is related to igneous processes. This is because wrinkle ridges are mostly associated in space and possibly in time with the occurrence of flood-basalt volcanism in all cases on the rocky bodies in the inner solar system. To address this issue, we conducted geomorphological mapping, a topographic-data analysis, and a detailed landform analysis of satellite images at a resolution of 25 cm/pixel to 6 m/pixel in the central Tharsis region of Mars. The main results of this work are in the form of (1) a regional geomorphological map at a resolution of 6 m/pixel and (2) a local geomorphological map at a resolution of 50 cm/pixel. Our work suggests the following sequence of geological events in the study area: (1) formation of a northeast-trending mountain range (i.e., the Thaumasia plateau) along the eastern margin of the Tharsis rise resulting from the Himalayan-style crustal-scale thrusting; (2) coeval volcanic-plateau construction west of the thrusting-induced rising mountain range; (3) termination of east-flowing lavas sourced from the volcanic plateau at the rising mountain range to the east; (4) wrinkle-ridge development by folding in recently emplaced warm, ductile volcanic-lava piles; (5) emplacement of a regionally extensive ice sheet over the central Tharsis region that produced extensive boulder-bearing materials, striated surfaces, and boulder-bearing dendritic-ridge networks possibly representing glacial eskers; and (6) deposition of locally highly concentrated glacial flours during deglaciation that resulted in the formation of mantled terrain on plains between wrinkle ridges. Our work supports the early suggestion that the Tharsis wrinkle ridges were created by horizontal shortening induced by crustal-scale tectonic processes. In detail, however, the occurrence of flow-front-like margins of many mapped wrinkle ridges suggests their formation by ductile deformation, which we attribute to the thermally weakened lava piles emplaced during or immediately before the folding event. Our compression-induced wrinkle-ridge model also differs from the early hypotheses in that the thin-skinned folding is associated with basement subduction, which explains the lack of coeval and parallel folding and extensional faulting. Post-folding glacial modification means that the present wrinkle-ridge morphologies may differ significantly from the original fold shapes, which prevents the utility of using present-day topographic profiles across wrinkle ridges for inverting the underlying thrust geometries.

Self-Assembly, Self-Folding, and Origami: Comparative Design Principles

Self-assembly is usually considered a parallel process while self-folding and origami are usually considered to be serial processes. We believe that these distinctions do not hold in actual experiments. Based upon our experience with 4D printing, we have developed three additional hybrid classes: (1) templated-assisted (tethered) self-assembly: e.g., when RNA is bound to viral capsomeres, the subunits are constricted in their interactions to have aspects of self-folding as well; (2) self-folding can depend upon interactions with the environment; for example, a protein synthesized on a ribosome will fold as soon as peptides enter the intracellular environment in a serial process whereas if denatured complete proteins are put into solution, parallel folding can occur simultaneously; and, (3) in turbulent environments, chaotic conditions continuously alternate processes. We have examined the 43,380 Dürer nets of dodecahedra and 43,380 Dürer nets of icosahedra and their corresponding duals: Schlegel diagrams. In order to better understand models of self-assembly of viral capsids, we have used both geometric (radius of gyration, convex hulls, angles) and topological (vertex connections, leaves, spanning trees, cutting trees, and degree distributions) perspectives to develop design principles for 4D printing experiments. Which configurations fold most rapidly? Which configurations lead to complete polyhedra most of the time? By using Hamiltonian circuits of the vertices of Dürer nets and Eulerian paths of cutting trees of polyhedra unto Schlegel diagrams, we have been able to develop a systematic sampling procedure to explore the 86,760 configurations, models of a T1 viral capsid with 60 subunits and to test alternatives with 4D printing experiments, use of MagformsTM, and origami models to demonstrate via movies the five processes described above.

Ag-catalyzed GaSb nanowires for flexible near-infrared photodetectors

High-quality narrow bandgap semiconductors nanowires (NWs) challenge the flexible near-infrared (NIR) photodetectors in next-generation imaging, data communication, environmental monitoring, and bioimaging applications. In this work, complementary metal oxide semiconductor-compatible metal of Ag is deposited on glass as the growth catalyst for the surfactant-assisted chemical vapor deposition of GaSb NWs. The uniform morphology, balance stoichiometry, high-quality crystallinity, and phase purity of as-prepared NWs are checked by scanning electron microscopy, energy dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, and X-ray diffraction. The electrical properties of as-prepared NWs are studied by constructing back-gated field-effect-transistors, displaying a high I on/I off ratio of 104 and high peak hole mobility of 400 cm2/(V·s). Benefiting from the excellent electrical and mechanical flexibility properties, the as-fabricated NW flexible NIR photodetector exhibits high sensitivity and excellent photoresponse, with responsivity as high as 618 A/W and detectivity as high as 6.7 × 1010 Jones. Furthermore, there is no obvious decline in NIR photodetection behavior, even after parallel and perpendicular folding with 1200 cycles.

Lid Margin Score Is the Strongest Predictor of Meibomian Area Loss.

Although meibography provides direct evidence of gland dropout in meibomian gland dysfunction, this specialized technique is not available in most clinics. The primary aim was to determine which clinical ocular marker was most related to meibomian area loss. A secondary aim was to determine associations with confocal microscopy imaging of the lid margin. One hundred participants from age 18 to 65 years were recruited. Measurements of the right eye and its upper eyelid, where relevant, included noninvasive tear break-up time, bulbar and limbal redness scores, blepharitis score, lipid layer thickness, number of parallel conjunctival folds, tear osmolarity, corneal fluorescein staining, phenol red thread test, lid margin score, meibography, and in vivo confocal microscopy. Participants also completed the Ocular Surface Disease Index questionnaire. The relationships between the measurements were determined using the Spearman correlation. The receiver operating characteristic curve and area under the receiver operating characteristic curve were used to determine the cutoff value of clinical markers. Significant correlations were found between meibomian area and lid margin score (r = -0.47, P < 0.01), and meibomian tortuosity and lid signs of blepharitis (r = -0.32, P < 0.01). Area under the receiver operating characteristic curve analysis revealed that a lid margin score of ≥1.70 detected meibomian area loss with a sensitivity of 0.58 and a specificity of 0.86. There were significant correlations between meibomian area and orifice area at 30 μm depth (r = -0.25, P = 0.01). The lid margin score was most related to the meibomian area and thus the best predictor of undiagnosed meibomian area loss.

Engineering a Hyperstable Yersinia pestis Outer Membrane Protein Ail Using Thermodynamic Design.

Development of viable therapeutics to effectively combat tier I pneumopathogens such as Yersinia pestis requires a thorough understanding of proteins vital for pathogenicity. The host invasion protein Ail, although indispensable for Yersinia pathogenesis, has evaded detailed characterization, as it is an outer membrane protein with intrinsically low stability and high aggregation propensity. Here, we identify molecular elements of the metastable Ail structure that considerably alter protein-lipid and intraprotein thermodynamics. In addition, we find that four residues Q50, L88, L92, and A94 contribute additively to the lowered stability of Ail, and their conserved substitution is sufficient to re-engineer Ail to Out14, a thermodynamically hyperstable low-aggregation variant with a functional scaffold. Interestingly, Ail also shows two (parallel) folding pathways, which has not yet been reported for β-barrel membrane proteins. Additionally, we identify the molecular mechanism of enhanced thermodynamic stability of Out14. We show that this enhanced stability of Out14 is due to a favorable change in the nonpolar accessible surface, and the accumulation of a kinetically accelerated off-pathway folding intermediate, which is absent in wild-type Ail. Such engineered hyperstable Ail β-barrels can be harnessed for targeted drug screening and developing medical countermeasures against Yersiniae. Application of similar strategies will help design effective translational therapeutics to combat biopathogens.

Resolving the fine structure in the energy landscapes of repeat proteins.

Ankyrin (ANK) repeat proteins are coded by tandem occurrences of patterns with around 33 amino acids. They often mediate protein-protein interactions in a diversity of biological systems. These proteins have an elongated non-globular shape and often display complex folding mechanisms. This work investigates the energy landscape of representative proteins of this class made up of 3, 4 and 6 ANK repeats using the energy-landscape visualisation method (ELViM). By combining biased and unbiased coarse-grained molecular dynamics AWSEM simulations that sample conformations along the folding trajectories with the ELViM structure-based phase space, one finds a three-dimensional representation of the globally funnelled energy surface. In this representation, it is possible to delineate distinct folding pathways. We show that ELViMs can project, in a natural way, the intricacies of the highly dimensional energy landscapes encoded by the highly symmetric ankyrin repeat proteins into useful low-dimensional representations. These projections can discriminate between multiplicities of specific parallel folding mechanisms that otherwise can be hidden in oversimplified depictions.

The mechanical analysis of parallel folding of cerebellum depending on oriented nerve fibers

The mechanical analysis of parallel folding of cerebellum depending on oriented nerve fibers

Hidden intermediates in Mango III RNA aptamer folding revealed by pressure perturbation

Fluorescent RNA aptamers have the potential to enable routine quantitation and localization of RNA molecules and serve as models for understanding biologically active aptamers. In recent years, several fluorescent aptamers have been selected and modified to improve their properties, revealing that small changes to the RNA or the ligands can modify significantly their fluorescent properties. Although structural biology approaches have revealed the bound, ground state of several fluorescent aptamers, characterization of low-abundance, excited states in these systems is crucial to understanding their folding pathways. Here we use pressure as an alternative variable to probe the suboptimal states of the Mango III aptamer with both fluorescence and NMR spectroscopy approaches. At moderate KCl concentrations, increasing pressure disrupted the G-quadruplex structure of the Mango III RNA and led to an intermediate with lower fluorescence. These observations indicate the existence of suboptimal RNA structural states that still bind the TO1-biotin fluorophore and moderately enhance fluorescence. At higher KCl concentration as well, the intermediate fluorescence state was populated at high pressure, but the G-quadruplex remained stable at high pressure, supporting the notion of parallel folding and/or binding pathways. These results demonstrate the usefulness of pressure for characterizing RNA folding intermediates.

Age and structural constraints on the tectonic evolution of the Paleoproterozoic Saimaa orocline in Fennoscandia

The Paleoproterozoic oroclines of Fennoscandia played a vital role in the making of continental equidimensional crust during the Svecofennian orogeny. We propose that the 1.90–1.88 Ga arc rocks in south-central Finland originally formed a single linear arc system that is now represented by the coupled Bothnian oroclines and their southern continuation, the Saimaa orocline, as defined in this study. A regional large-scale approach with robust geochronological age determinations obtained from metasedimentary rocks and granitoids, and field-based structural studies are used to produce a coherent view on the tectonic evolution of the Saimaa orocline.The pre-orocline tectonic evolution started with a NE-SW collision between the Karelia continent (lower plate) and Proto-Svecofennia (upper plate) at ca. 1.91 Ga (D1). This was followed by subduction reversal and arc magmatism at ca. 1.90–1.88 Ga. Collision or flat subduction at 1.885 Ga caused a widespread collisional event (D2). Our results indicate that the presently E-W oriented D2 structures are not, as is widely proposed, products of N-S contraction but instead originated as a N-S to NNW-SSE oriented belt that was subject to E-W contraction. Dorocline, recorded as the first deformation stage in post-D2 sediments, folded the pre-existing structures into their E-W and ENE-WSW orientation. Following orocline formation, the main shortening direction switched back to the NE-SW (D3) resulting in type-1 and type-2 refolded folds, long wavelength regional folds and bending of the hinge zone of the Saimaa orocline. D4-D5 deformation stages are localized intra-continental tectonic events at 1.83–1.79 Ga. The formation of the Saimaa orocline is bracketed at 1875–1865 Ma and formed by margin-parallel shortening. The Bothnian and Saimaa oroclines form continuous buckles, but whereas the Bothnian coupled oroclines are crustal-scale parallel folds due to more rigid crustal core, Keitele microcontinent, the Saimaa orocline is a crustal-scale isoclinal similar fold.