Contact Restraints Research Articles

Analysis of Stress-Strain State and Contact Pressures on Surfaces of Kaplan Runner Blade Bearing Bronze Bushes

An analysis of the existing and prospective blade seal designs for Kaplan runners was performed. The selected design type provides the maximum ecological safety for Kaplan runners. A 3D model of runner hub sector with the trunnion, inner and outer bushes of blade trunnion was generated taking into account the cyclic symmetry of the runner design based on the modern automated design engineering system. A diagram of application of external loads from the blade and lever to the given 3D model of the Kaplan runner hub segment was developed. The contact problem was formulated to determine the stress-strain state as well as the contact pressures at the inner and outer bronze bushes of the Kaplan runner blade trunnions in different operating conditions. The problem was formulated for the finite element method, taking into consideration the diagram of external load application and contact restraints to the given 3D model of the Kaplan runner hub sector in the software package for engineering calculations. Using calculation results, principal stress distribution diagrams and the distribution diagram for the contact pressure at the outer and inner bronze bushes of blade trunnions were obtained. Strength calculation results were processed using the data of principal stress distribution diagrams, and the contact pressure values at the inner and outer bronze bushes of blade trunnions were determined. A methodology for further use of the given analytical model in the evaluation of stress-strain state of Kaplan runners involving modern automated design engineering systems and software package for engineering calculations was developed. The comparison of stress-strain states of the blade trunnion bushes was performed for the old and new designs of the Kaplan runner seal.

Modeling protein structures with the coarse-grained UNRES force field in the CASP14 experiment

The UNited RESidue (UNRES) force field was tested in the 14th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP14), in which larger oligomeric and multimeric targets were present compared to previous editions. Three prediction modes were tested (i) ab initio (the UNRES group), (ii) contact-assisted (the UNRES-contact group), and (iii) template-assisted (the UNRES-template group). For most of the targets, the contact restraints were derived from the server models top-ranked by the DeepQA method, while the DNCON2 method was used for 11 targets. Our consensus-fragment procedure was used to run template-assisted predictions. Each group also processed the Nuclear Magnetic Resonance (NMR)- and Small Angle X-Ray Scattering (SAXS)-data assisted targets. The average Global Distance Test Total Score (GDT_TS) of the ‘Model 1’ predictions were 29.17, 39.32, and 56.37 for the UNRES, UNRES-contact, and UNRES-template predictions, respectively, increasing by 0.53, 2.24, and 3.76, respectively, compared to CASP13. It was also found that the GDT_TS of the UNRES models obtained in ab initio mode and in the contact-assisted mode decreases with the square root of chain length, while the exponent in this relationship is 0.20 for the UNRES-template group models and 0.11 for the best performing AlphaFold2 models, which suggests that incorporation of database information, which stems from protein evolution, brings in long-range correlations, thus enabling the correction of force-field inaccuracies.

Deep-learning contact-map guided protein structure prediction in CASP13.

We report the results of two fully automated structure prediction pipelines, "Zhang-Server" and "QUARK", in CASP13. The pipelines were built upon the C-I-TASSER and C-QUARK programs, which in turn are based on I-TASSER and QUARK but with three new modules: (a) a novel multiple sequence alignment (MSA) generation protocol to construct deep sequence-profiles for contact prediction; (b) an improved meta-method, NeBcon, which combines multiple contact predictors, including ResPRE that predicts contact-maps by coupling precision-matrices with deep residual convolutional neural-networks; and (c) an optimized contact potential to guide structure assembly simulations. For 50 CASP13 FM domains that lacked homologous templates, average TM-scores of the first models produced by C-I-TASSER and C-QUARK were 28% and 56% higher than those constructed by I-TASSER and QUARK, respectively. For the first time, contact-map predictions demonstrated usefulness on TBM domains with close homologous templates, where TM-scores of C-I-TASSER models were significantly higher than those of I-TASSER models with a P-value <.05. Detailed data analyses showed that the success of C-I-TASSER and C-QUARK was mainly due to the increased accuracy of deep-learning-based contact-maps, as well as the careful balance between sequence-based contact restraints, threading templates, and generic knowledge-based potentials. Nevertheless, challenges still remain for predicting quaternary structure of multi-domain proteins, due to the difficulties in domain partitioning and domain reassembly. In addition, contact prediction in terminal regions was often unsatisfactory due to the sparsity of MSAs. Development of new contact-based domain partitioning and assembly methods and training contact models on sparse MSAs may help address these issues.

Introduction of a bounded penalty function in contact-assisted simulations of protein structures to omit false restraints.

Contact-assisted simulations, the contacts being predicted or determined experimentally, have become very important in the determination of the structures of proteins and other biological macromolecules. In this work, the effect of contact-distance restraints on the simulated structures was investigated with the use of multiplexed replica exchange simulations with the coarse-grained UNRES force field. A modified bounded flat-bottom restraint function that does not generate a gradient when a restraint cannot be satisfied was implemented. Calculations were run with (i) a set of four small proteins, with contact restraints derived from experimental structures, and (ii) selected CASP11 and CASP12 targets, with restraints as used at prediction time. The bounded penalty function largely omitted false contacts, which were usually inconsistent. It was found that at least 20% of correct contacts must be present in the restraint set to improve model quality with respect to unrestrained simulations. © 2019 Wiley Periodicals, Inc.

Template-based and free modeling of I-TASSER and QUARK pipelines using predicted contact maps in CASP12.

We develop two complementary pipelines, "Zhang-Server" and "QUARK", based on I-TASSER and QUARK pipelines for template-based modeling (TBM) and free modeling (FM), and test them in the CASP12 experiment. The combination of I-TASSER and QUARK successfully folds three medium-size FM targets that have more than 150 residues, even though the interplay between the two pipelines still awaits further optimization. Newly developed sequence-based contact prediction by NeBcon plays a critical role to enhance the quality of models, particularly for FM targets, by the new pipelines. The inclusion of NeBcon predicted contacts as restraints in the QUARK simulations results in an average TM-score of 0.41 for the best in top five predicted models, which is 37% higher than that by the QUARK simulations without contacts. In particular, there are seven targets that are converted from non-foldable to foldable (TM-score >0.5) due to the use of contact restraints in the simulations. Another additional feature in the current pipelines is the local structure quality prediction by ResQ, which provides a robust residue-level modeling error estimation. Despite the success, significant challenges still remain in ab initio modeling of multi-domain proteins and folding of β-proteins with complicated topologies bound by long-range strand-strand interactions. Improvements on domain boundary and long-range contact prediction, as well as optimal use of the predicted contacts and multiple threading alignments, are critical to address these issues seen in the CASP12 experiment.

Partial unfolding and refolding for structure refinement: A unified approach of geometric simulations and molecular dynamics.

The most successful protein structure prediction methods to date have been template-based modeling (TBM) or homology modeling, which predicts protein structure based on experimental structures. These high accuracy predictions sometimes retain structural errors due to incorrect templates or a lack of accurate templates in the case of low sequence similarity, making these structures inadequate in drug-design studies or molecular dynamics simulations. We have developed a new physics based approach to the protein refinement problem by mimicking the mechanism of chaperons that rehabilitate misfolded proteins. The template structure is unfolded by selectively (targeted) pulling on different portions of the protein using the geometric based technique FRODA, and then refolded using hierarchically restrained replica exchange molecular dynamics simulations (hr-REMD). FRODA unfolding is used to create a diverse set of topologies for surveying near native-like structures from a template and to provide a set of persistent contacts to be employed during re-folding. We have tested our approach on 13 previous CASP targets and observed that this method of folding an ensemble of partially unfolded structures, through the hierarchical addition of contact restraints (that is, first local and then nonlocal interactions), leads to a refolding of the structure along with refinement in most cases (12/13). Although this approach yields refined models through advancement in sampling, the task of blind selection of the best refined models still needs to be solved. Overall, the method can be useful for improved sampling for low resolution models where certain of the portions of the structure are incorrectly modeled.

An upwind least square formulation for free surfaces calculation of viscoplastic steady-state metal forming problems

Despite using very large parallel computers, numerical simulation of some forming processes such as multi-pass rolling, extrusion or wire drawing, need long computation time due to the very large number of time steps required to model the steady regime of the process. The direct calculation of the steady-state, whenever possible, allows reducing by 10–20 the computational effort. However, removing time from the equations introduces another unknown, the steady final shape of the domain. Among possible ways to solve this coupled multi-fields problem, this paper selects a staggered fixed-point algorithm that alternates computation of mechanical fields on a prescribed domain shape with corrections of the domain shape derived from the velocity field and the stationary condition v.n = 0. It focuses on the resolution of the second step in the frame of unstructured 3D meshes, parallel computing with domain partitioning, and complex shapes with strong contact restraints. To insure these constraints a global finite elements formulation is used. The weak formulation based on a Galerkin method of the v.n = 0 equation is found to diverge in severe tests cases. The least squares formulation experiences problems in the presence of contact restraints, upwinding being shown necessary. A new upwind least squares formulation is proposed and evaluated first on analytical solutions. Contact being a key issue in forming processes, and even more with steady formulations, a special emphasis is given to the coupling of contact equations between the two problems of the staggered algorithm, the thermo-mechanical and free surface problems. The new formulation and algorithm is finally applied to two complex actual metal forming problems of rolling. Its accuracy and robustness with respect to the shape initialization of the staggered algorithm is discussed, and its efficiency is compared to non-steady simulations.

CONFOLD: Residue-residue contact-guided ab initio protein folding.

Predicted protein residue-residue contacts can be used to build three-dimensional models and consequently to predict protein folds from scratch. A considerable amount of effort is currently being spent to improve contact prediction accuracy, whereas few methods are available to construct protein tertiary structures from predicted contacts. Here, we present an ab initio protein folding method to build three-dimensional models using predicted contacts and secondary structures. Our method first translates contacts and secondary structures into distance, dihedral angle, and hydrogen bond restraints according to a set of new conversion rules, and then provides these restraints as input for a distance geometry algorithm to build tertiary structure models. The initially reconstructed models are used to regenerate a set of physically realistic contact restraints and detect secondary structure patterns, which are then used to reconstruct final structural models. This unique two-stage modeling approach of integrating contacts and secondary structures improves the quality and accuracy of structural models and in particular generates better β-sheets than other algorithms. We validate our method on two standard benchmark datasets using true contacts and secondary structures. Our method improves TM-score of reconstructed protein models by 45% and 42% over the existing method on the two datasets, respectively. On the dataset for benchmarking reconstructions methods with predicted contacts and secondary structures, the average TM-score of best models reconstructed by our method is 0.59, 5.5% higher than the existing method. The CONFOLD web server is available at http://protein.rnet.missouri.edu/confold/.

Static interactions of surface contacts in a fixture–workpiece system

Static indeterminacy and frictional constraint nonlinearity are common problems encountered in fixture configuration design. In a fixture–workpiece system, the behaviour of contact is influenced by a combination of geometrical, kinematic and elastic relationships. Our objective is to determine clamping force intensities for a given layout of fixels by investigating contact force distribution. In this paper, we present a numerical procedure to accurately determine clamping forces required to satisfy fixturing requirements with good computational efficiency. A system of virtual springs is used to illustrate the states of contact restraints at locating and clamping points. The differences between manual clamping and power clamping are investigated and analysed theoretically. A cone set of virtual springs is introduced to model a frictional contact. We then develop a linear programming model to find a set of minimum clamping force intensities, and to identify their feasible directions for increments. Examples are also given to demonstrate the procedure.

Algebraic test of relative form closure grasps with its implementation

This paper presents an approach to algebraic detection of relative form closure for a multi-fingered grasp G and gives an attention to the classification of relative form closures. Whether or not a grasp G is of relative form closure has been verified by the geometric criterion 0∈rintC[G] (Xiong Y L, Xiong X R. Algebraic structure and geometric interpretation of rigid complex fixture system. IEEE Trans Autom Sci Eng, 2007, 4: 252–264; Xiong Y L. Theory of point contact restraint and qualitative analysis of robot grasping. Sci China Ser A-Math, 1994, 37: 629–640). Our aim is at transferring the geometric criterion into an algebraic formulation by a theorem that a grasp G is relative form closure, if, and only if the origin 0 can be represented as a positive convex combination of G. So we develop a constructive procedure called ri-simplex algorithm to find a positive convex combination of G when it has relative form closure. Form closure is considered as a special case of relative form closure, when the grasp G can affinely span the whole space, while partly relative form closure is referred to as form closed relative to a subset G 1 of G.

Prediction, refinement, and persistency of transmembrane helix dimers in lipid bilayers using implicit and explicit solvent/lipid representations: Microsecond molecular dynamics simulations of ErbB1/B2 and EphA1

All-atom simulations are carried out on ErbB1/B2 and EphA1 transmembrane helix dimers in lipid bilayers starting from their solution/DMPC bicelle NMR structures. Over the course of microsecond trajectories, the structures remain in close proximity to the initial configuration and satisfy the majority of experimental tertiary contact restraints. These results further validate CHARMM protein/lipid force fields and simulation protocols on Anton. Separately, dimer conformations are generated using replica exchange in conjunction with an implicit solvent and lipid representation. The implicit model requires further improvement, and this study investigates whether lengthy all-atom molecular dynamics simulations can alleviate the shortcomings of the initial conditions. The simulations correct many of the deficiencies. For example, excessive helix twisting is eliminated over a period of hundreds of nanoseconds. The helix tilt, crossing angles, and dimer contacts approximate those of the NMR-derived structure, although the detailed contact surface remains off-set for one of two helices in both systems. Hence, even microsecond simulations are not long enough for extensive helix rotations. The alternate structures can be rationalized with reference to interaction motifs and may represent still sought after receptor states that are important in ErbB1/B2 and EphA1 signaling.

Improving Protein Structure Prediction Using Multiple Sequence-Based Contact Predictions

Although residue-residue contact maps dictate the topology of proteins, sequence-based ab initio contact predictions have been found little use in actual structure prediction due to the low accuracy. We developed a composite set of nine SVM-based contact predictors that are used in I-TASSER simulation in combination with sparse template contact restraints. When testing the strategy on 273 nonhomologous targets, remarkable improvements of I-TASSER models were observed for both easy and hard targets, with p value by Student's t test<0.00001 and 0.001, respectively. In several cases, template modeling score increases by >30%, which essentially converts "nonfoldable" targets into "foldable" ones. In CASP9, I-TASSER employed ab initio contact predictions, and generated models for 26 FM targets with a GDT-score 16% and 44% higher than the second and third best servers from other groups, respectively. These findings demonstrate a new avenue to improve the accuracy of protein structure prediction especially for free-modeling targets.

TASSER_WT: A Protein Structure Prediction Algorithm with Accurate Predicted Contact Restraints for Difficult Protein Targets

To improve the prediction accuracy in the regime where template alignment quality is poor, an updated version of TASSER_2.0, namely TASSER_WT, was developed. TASSER_WT incorporates more accurate contact restraints from a new method, COMBCON. COMBCON uses confidence-weighted contacts from PROSPECTOR_3.5, the latest version, PROSPECTOR_4, and a new local structural fragment-based threading algorithm, STITCH, implemented in two variants depending on expected fragment prediction accuracy. TASSER_WT is tested on 622 Hard proteins, the most difficult targets (incorrect alignments and/or templates and incorrect side-chain contact restraints) in a comprehensive benchmark of 2591 nonhomologous, single domain proteins ≤200 residues that cover the PDB at 35% pairwise sequence identity. For 454 of 622 Hard targets, COMBCON provides contact restraints with higher accuracy and number of contacts per residue. As contact coverage with confidence weight ≥3 ( F wt ≥3 cov ) increases, the more improved are TASSER_WT models. When F wt ≥3 cov > 1.0 and > 0.4, the average root mean-square deviation of TASSER_WT (TASSER_2.0) models is 4.11 Å (6.72 Å) and 5.03 Å (6.40 Å), respectively. Regarding a structure prediction as successful when a model has a TM-score to the native structure ≥0.4, when F wt ≥3 cov > 1.0 and > 0.4, the success rate of TASSER_WT (TASSER_2.0) is 98.8% (76.2%) and 93.7% (81.1%), respectively.

Validation of dynamic block displacement analysis and modification of edge-to-edge contact constraints in 3-D DDA

The validity of three-dimensional discontinuous deformation analysis (3-D DDA) is examined by comparing its solution for dynamic block displacement with an analytical solution. Displacement of a single block on inclined planes subjected to dynamic loadings is studied for analytical solutions derived with respect to the frictional resistance offered by the planes. 3-D DDA predicts accurately the analytical displacements, and the results were found sensitive to the maximum displacement ratio, and the size of the time step, which are defined by the user. Best results were achieved when the actual displacements were approximately equal to the assumed maximum displacements per time step. Furthermore, edge-to-edge contact constraints have been improved by using the augmented Lagrangian method instead of the penalty method. Using the augmented Lagrangian method to enforce contact restraints retains the simplicity of the penalty method, and reduces its disadvantages. The new formulation of edge-to-edge contact using the augmented Lagrangian method is implemented in 3-D DDA and has been programmed in VC++. Finally two illustrative examples are presented for demonstrating this new approach.

Benchmarking of TASSER_2.0: An Improved Protein Structure Prediction Algorithm with More Accurate Predicted Contact Restraints

To improve tertiary structure predictions of more difficult targets, the next generation of TASSER, TASSER_2.0, has been developed. TASSER_2.0 incorporates more accurate side-chain contact restraint predictions from a new approach, the composite-sequence method, based on consensus restraints generated by an improved threading algorithm, PROSPECTOR_3.5, which uses computationally evolved and wild-type template sequences as input. TASSER_2.0 was tested on a large-scale, benchmark set of 2591 nonhomologous, single domain proteins ≤200 residues that cover the Protein Data Bank at 35% pairwise sequence identity. Compared with the average fraction of accurately predicted side-chain contacts of 0.37 using PROSPECTOR_3.5 with wild-type template sequences, the average accuracy of the composite-sequence method increases to 0.60. The resulting TASSER_2.0 models are closer to their native structures, with an average root mean-square deviation of 4.99 Å compared to the 5.31 Å result of TASSER. Defining a successful prediction as a model with a root mean-square deviation to native <6.5 Å, the success rate of TASSER_2.0 (TASSER) for Medium targets (targets with good templates/poor alignments) is 74.3% (64.7%) and 40.8% (35.5%) for the Hard targets (incorrect templates/alignments). For Easy targets (good templates/alignments), the success rate slightly increases from 86.3% to 88.4%.

Three-Dimensional Structure of an Intact Glycoside Hydrolase Family 15 Glucoamylase from Hypocrea jecorina

The three-dimensional structure of a complete Hypocrea jecorina glucoamylase has been determined at 1.8 A resolution. The presented structure model includes the catalytic and starch binding domains and traces the course of the 37-residue linker segment. While the structures of other fungal and yeast glucoamylase catalytic and starch binding domains have been determined separately, this is the first intact structure that allows visualization of the juxtaposition of the starch binding domain relative to the catalytic domain. The detailed interactions we see between the catalytic and starch binding domains are confirmed in a second independent structure determination of the enzyme in a second crystal form. This second structure model exhibits an identical conformation compared to the first structure model, which suggests that the H. jecorina glucoamylase structure we report is independent of crystal lattice contact restraints and represents the three-dimensional structure found in solution. The proposed starch binding regions for the starch binding domain are aligned with the catalytic domain in the three-dimensional structure in a manner that supports the hypothesis that the starch binding domain serves to target the glucoamylase at sites where the starch granular matrix is disrupted and where the enzyme might most effectively function.

Development and benchmarking of TASSERiter for the iterative improvement of protein structure predictions

To improve the accuracy of TASSER models especially in the limit where threading provided template alignments are of poor quality, we have developed the TASSER(iter) algorithm which uses the templates and contact restraints from TASSER generated models for iterative structure refinement. We apply TASSER(iter) to a large benchmark set of 2,773 nonhomologous single domain proteins that are < or = 200 in length and that cover the PDB at the level of 35% pairwise sequence identity. Overall, TASSER(iter) models have a smaller global average RMSD of 5.48 A compared to 5.81 A RMSD of the original TASSER models. Classifying the targets by the level of prediction difficulty (where Easy targets have a good template with a corresponding good threading alignment, Medium targets have a good template but a poor alignment, and Hard targets have an incorrectly identified template), TASSER(iter) (TASSER) models have an average RMSD of 4.15 A (4.35 A) for the Easy set and 9.05 A (9.52 A) for the Hard set. The largest reduction of average RMSD is for the Medium set where the TASSER(iter) models have an average global RMSD of 5.67 A compared to 6.72 A of the TASSER models. Seventy percent of the Medium set TASSER(iter) models have a smaller RMSD than the TASSER models, while 63% of the Easy and 60% of the Hard TASSER models are improved by TASSER(iter). For the foldable cases, where the targets have a RMSD to the native <6.5 A, TASSER(iter) shows obvious improvement over TASSER models: For the Medium set, it improves the success rate from 57.0 to 67.2%, followed by the Hard targets where the success rate improves from 32.0 to 34.8%, with the smallest improvement in the Easy targets from 82.6 to 84.0%. These results suggest that TASSER(iter) can provide more reliable predictions for targets of Medium difficulty, a range that had resisted improvement in the quality of protein structure predictions.

Quantitative Analysis of Inner Force Distribution and Load Capacity of Grasps and Fixtures

This paper focuses on a quantitative analysis for grasp planning and fixture design based on an analytical description of point contact restraint. In the framework, the analysis deals with the fundamental concepts of restraint cone, freedom cone, force-determinacy and relative form closure. A method is presented to quantify the performance of a fixture (or grasp) with two major characteristics of inner force distribution and load capacity. Two different fixturing (or grasp) models of simplex grasp and elastic grasp are presented. It is shown that the performance of these two types of grasp (or fixturing) could be measured with different performance indices. A minimax index (MMI) and a volume measure are defined for evaluating a simplex grasp, while a measure using the tolerable range of differential motion in the twist space or the allowable load polyhedron in the wrench space would be suitable for quantifying robustness and load capability of an elastic fixture system. Furthermore, for fixture system design a geometric analysis and reasoning procedure is described for the design of locators, clamps and supplementary supports. The aim of these proposed analysis and design techniques is to provide a scientific foundation for automated grasping/fixturing system design in the engineering practice.

Theory of Point Contact Restraint and Qualitative Analysis of Robot Grasping

This paper presents a geometrical representation of robot grasping and a definition of relative form closure of point contact restraint based on the concepts of positive linear combination,affine combination,convex combination,etc.in the screw space.The dual equivalence theorem,topological equivalence theorem and algebraic equivalence theorem are derived from the defined restraint cone and freedom cone in the dual screw spaces.A J0-function method of computer-aided grasp planning is implemented more efficiently than other proposed methods.The states of restraint and instantaneous motion of a rigid body grasped by a set of point contacts are specified by the unisense degrees of freedom and unisense degrees of restraint.Finally,a quality measure of robot grasping is provided for the synthesis procedure of relatively form-closed grasp.

Optimal Synthesis of Point Contact Restraint

The object of this paper is to develop a procedure that will allow the establishment of necessary and sufficient point contacts on a rigid body to ensure that the body has any desired state of instantaneous motion or restraint. The screw space and its sub-spaces are employed; these are vector spaces but not Euclidean spaces. The states of restraint and instantaneous motion of a body restrained by a system of screws of point contacts are specified by reciprocal sub-spaces of the screw space. This leads to a synthesis procedure for restraint of a rigid body by means of point contacts. The existence and uniqueness of the synthesis solution are discussed, and necessary and sufficient conditions for a realizable surface of a kinematic pair are given. Finally, two quality measures for a feasible set of screws are defined. One represents the uniformity of the distribution of internal forces while the other indicates the restraint's ability to resist external forces.