Accurate De Novo Prediction of Protein Contact Map by Ultra-Deep Learning Model

Recently exciting progress has been made on protein contact prediction, but the predicted contacts for proteins without many sequence homologs is still of low quality and not very useful for de novo structure prediction. This paper presents a new deep learning method that predicts contacts by integrating both evolutionary coupling (EC) and sequence conservation information through an ultra-deep neural network formed by two deep residual networks. This deep neural network allows us to model very complex sequence-contact relationship as well as long-range inter-contact correlation. Our method greatly outperforms existing contact prediction methods and leads to much more accurate contact-assisted protein folding. Tested on three datasets of 579 proteins, the average top L long-range prediction accuracy obtained our method, the representative EC method CCMpred and the CASP11 winner MetaPSICOV is 0.47, 0.21 and 0.30, respectively; the average top L/10 long-range accuracy of our method, CCMpred and MetaPSICOV is 0.77, 0.47 and 0.59, respectively. Ab initio folding using our predicted contacts as restraints can yield correct folds (i.e., TMscore>0.6) for 203 test proteins, while that using MetaPSICOV- and CCMpred-predicted contacts can do so for only 79 and 62 proteins, respectively. Further, our contact-assisted models have much better quality than template-based models. Using our predicted contacts as restraints, we can (ab initio) fold 208 of the 398 membrane proteins with TMscore>0.5. By contrast, when the training proteins of our method are used as templates, homology modeling can only do so for 10 of them. One interesting finding is that even if we do not train our prediction models with any membrane proteins, our method works very well on membrane protein prediction. Finally, in recent blind CAMEO benchmark our method successfully folded 5 test proteins with a novel fold

Predicting Secondary Structures, Contact Numbers, and Residue-wise Contact Orders of Native Protein Structure from Amino Acid Sequence by Critical Random Networks

Prediction of one-dimensional protein structures such as secondary structures and contact numbers is useful for the three-dimensional structure prediction and important for the understanding of sequence-structure relationship. Here we present a new machine-learning method, critical random networks (CRNs), for predicting one-dimensional structures, and apply it, with position-specific scoring matrices, to the prediction of secondary structures (SS), contact numbers (CN), and residue-wise contact orders (RWCO). The present method achieves, on average, $Q_3$ accuracy of 77.8% for SS, correlation coefficients of 0.726 and 0.601 for CN and RWCO, respectively. The accuracy of the SS prediction is comparable to other state-of-the-art methods, and that of the CN prediction is a significant improvement over previous methods. We give a detailed formulation of critical random networks-based prediction scheme, and examine the context-dependence of prediction accuracies. In order to study the nonlinear and multi-body effects, we compare the CRNs-based method with a purely linear method based on position-specific scoring matrices. Although not superior to the CRNs-based method, the surprisingly good accuracy achieved by the linear method highlights the difficulty in extracting structural features of higher order from amino acid sequence beyond that provided by the position-specific scoring matrices.Comment: 20 pages, 1 figure, 5 tables; minor revision; accepted for publication in BIOPHYSIC

On adaptive mesh refinement in wrinkling prediction analysis

Hutchinson approach has been successfully used by a number of researchers in thin sheet metal forming processes for wrinkling prediction. However, Hutchinson approach is limited to regions of the sheet that are free of any contact. Therefore, a new wrinkling indicator that can be used in the contact areas is proposed. Discretisation error indicators are also used to present a comprehensive approach to wrinkling prediction analysis

Controlling wetting with electrolytic solutions: phase-field simulations of a droplet-conductor system

The wetting properties of immiscible two-phase systems are crucial in a wide range of applications, from lab-on-a-chip devices to field-scale oil recovery. It has long been known that effective wetting properties can be altered by the application of an electric field; a phenomenon coined as electrowetting. Here, we consider theoretically and numerically a single droplet sitting on an (insulated) conductor, i.e., within a capacitor. The droplet consists of a pure phase without solutes, while the surrounding fluid contains a symmetric monovalent electrolyte, and the interface between them is impermeable. Using nonlinear Poisson--Boltzmann theory, we present a theoretical prediction of the dependency of the apparent contact angle on the applied electric potential. We then present well-resolved dynamic simulations of electrowetting using a phase-field model, where the entire two-phase electrokinetic problem, including the electric double layers (EDLs), is resolved. The simulations show that, while the contact angle on scales smaller than the EDL is unaffected by the application of an electric field, an apparent contact angle forms on scales beyond the EDL. This contact angle relaxes in time towards a saturated apparent contact angle. The dependency of the contact angle upon applied electric potential is in good compliance with the theoretical prediction. The only phenomenological parameter in the prediction is shown to only depend on the permeability ratio between the two phases. Based on the resulting unified description, we obtain an effective expression of the contact angle which can be used in more macroscopic numerical simulations, i.e. where the electrokinetic problem is not fully resolved

Theoretical and experimental study of thermal contact resistance in a vacuum environment Semiannual status report no. 8, Jun. - Dec. 1965

Thermal contact resistance in vacuum environment using model prediction

Enhancing Bayesian risk prediction for epidemics using contact tracing

Contact tracing data collected from disease outbreaks has received relatively little attention in the epidemic modelling literature because it is thought to be unreliable: infection sources might be wrongly attributed, or data might be missing due to resource contraints in the questionnaire exercise. Nevertheless, these data might provide a rich source of information on disease transmission rate. This paper presents novel methodology for combining contact tracing data with rate-based contact network data to improve posterior precision, and therefore predictive accuracy. We present an advancement in Bayesian inference for epidemics that assimilates these data, and is robust to partial contact tracing. Using a simulation study based on the British poultry industry, we show how the presence of contact tracing data improves posterior predictive accuracy, and can directly inform a more effective control strategy.Comment: 40 pages, 9 figures. Submitted to Biostatistic

On the optimal contact potential of proteins

We analytically derive the lower bound of the total conformational energy of a protein structure by assuming that the total conformational energy is well approximated by the sum of sequence-dependent pairwise contact energies. The condition for the native structure achieving the lower bound leads to the contact energy matrix that is a scalar multiple of the native contact matrix, i.e., the so-called Go potential. We also derive spectral relations between contact matrix and energy matrix, and approximations related to one-dimensional protein structures. Implications for protein structure prediction are discussed.Comment: 5 pages, text onl

Efficient Humanoid Contact Planning using Learned Centroidal Dynamics Prediction

Humanoid robots dynamically navigate an environment by interacting with it via contact wrenches exerted at intermittent contact poses. Therefore, it is important to consider dynamics when planning a contact sequence. Traditional contact planning approaches assume a quasi-static balance criterion to reduce the computational challenges of selecting a contact sequence over a rough terrain. This however limits the applicability of the approach when dynamic motions are required, such as when walking down a steep slope or crossing a wide gap. Recent methods overcome this limitation with the help of efficient mixed integer convex programming solvers capable of synthesizing dynamic contact sequences. Nevertheless, its exponential-time complexity limits its applicability to short time horizon contact sequences within small environments. In this paper, we go beyond current approaches by learning a prediction of the dynamic evolution of the robot centroidal momenta, which can then be used for quickly generating dynamically robust contact sequences for robots with arms and legs using a search-based contact planner. We demonstrate the efficiency and quality of the results of the proposed approach in a set of dynamically challenging scenarios