Systematic Bottom-Up Molecular Coarse-Graining via Force Matching using Anisotropic Particles

We derive a systematic and general method for parametrizing coarse-grained molecular models consisting of anisotropic particles from fine-grained (e.g. all-atom) models for condensed-phase molecular dynamics simulations. The method, which we call anisotropic force-matching coarse-graining (AFM-CG), is based on rigorous statistical mechanical principles, enforcing consistency between the coarse-grained and fine-grained phase-space distributions to derive equations for the coarse-grained forces, masses, and moments of inertia in terms of properties of a condensed-phase fine-grained system. We verify the accuracy and efficiency of the method by coarse-graining liquid-state systems of two different anisotropic organic molecules, benzene and perylene, and show that the parametrized coarse-grained models more accurately describe properties of these systems than previous anisotropic coarse-grained models parametrized using other methods that do not account for finite-temperature and many-body effects on the condensed-phase coarse-grained interactions. The AFM-CG method will be useful for developing accurate and efficient dynamical simulation models of condensed-phase systems of molecules consisting of large, rigid, anisotropic fragments, such as nucleic acids, liquid crystals, and organic semiconductors.

Increased upper-limb sensory attenuation with age

The pressure of our own finger on the arm feels differently than the same pressure exerted by an external agent: the latter involves just touch, whereas the former involves a combination of touch and predictive output from the internal model of the body. This internal model predicts the movement of our own finger and hence the intensity of the sensation of the finger press is decreased. A decrease in intensity of the self-produced stimulus is called sensory attenuation. It has been reported that, due to decreased proprioception with age and an increased reliance on the prediction of the internal model, sensory attenuation is increased in older adults. In this study, we used a force-matching paradigm to test if sensory attenuation is also present over the arm and if aging increases sensory attenuation. We demonstrated that, while both young and older adults overestimate a self-produced force, older adults overestimate it even more showing an increased sensory attenuation. In addition, we also found that both younger and older adults self-produce higher forces when activating the homologous muscles of the upper limb. While this is traditionally viewed as evidence for an increased reliance on internal model function in older adults because of decreased proprioception, proprioception appeared unimpaired in our older participants. This begs the question of whether an age-related decrease in proprioception is really responsible for the increased sensory attenuation observed in older people.

Mixing ReaxFF parameters for transition metal oxides using force-matching method

We present the development of the method for the refitting the ReaxFF parameters for a system consisting of the mixed transition metal oxides. We have tested several methods allowing to calculate the differences between the vectors of the forces acting on atoms obtained from the reference DFT simulation and the parameters-dependent ReaxFF. We conclude that the footrule method yields the best parameters among the investigated options. We then validate the parameters using the system consisting of the hematite supported (TiO2)n clusters. The results indicate the refitted parameters allow to obtain acceptable geometries of the clusters upon MD simulation on the ReaxFF level, and despite the short timescale lead to the stable structures.

A Single Bout of High-Intensity Cardiovascular Exercise Does Not Enhance Motor Performance and Learning of a Visuomotor Force Modulation Task, but Triggers Ipsilateral Task-Related EEG Activity

Acute cardiovascular exercise (aCE) seems to be a promising strategy to improve motor performance and learning. However, results are heterogeneous, and the related neurophysiological mechanisms are not well understood. Oscillatory brain activitiy, such as task-related power (TRPow) in the alpha and beta frequencies, are known neural signatures of motor activity. Here, we tested the effects of aCE on motor performance and learning, along with corresponding modulations in EEG TRPow over the sensorimotor cortex. Forty-five right-handed participants (aged 18–34 years) practiced a visuomotor force-matching (FM) task after either high-intensity (HEG), low-intensity (LEG), or no exercise (control group, CG). Motor performance was assessed immediately, 15 min, 30 min, and 24 h after aCE/control. EEG was measured during the FM task. Results of frequentist and Bayesian statistics revealed that high- and low-intensity aCE had no effect at the behavioral level, adding to the previous mixed results. Interestingly, EEG analyses showed an effect of aCE on the ipsilateral sensorimotor cortex, with a stronger decrease in β-TRPow 15 min after exercise in both groups compared to the CG. Overall, aCE applied before motor practice increased ipsilateral sensorimotor activity, while motor learning was not affected; it remains to be seen whether aCE might affect motor learning in the long run.

Inter-Limb Asymmetry in Force Accuracy and Steadiness Changes after a 12-Week Strength Training Program in Young Healthy Men

The study aimed to investigate the impact of a 12-week strength training program on force accuracy and steadiness changes in lower limbs in young healthy men. Twenty subjects with a dominant right lower limb were included. They performed a force matching task both pre and post strength training program. The ability to reproduce force was determined by calculating three errors: absolute error (AE), constant error (CE), and variable error (VE). After intervention AE and VE improved in both legs indicating higher improvement in the dominant leg (p = 0.032 for AE and p = 0.005 for VE). However, CE improved only in the dominant leg (p = 0.001). We conclude that strength training improved the accuracy and consistency of force in a force reproduction task. This improvement was more evident in the dominant lower limb. Most likely, the inter-limb asymmetry in changes of force application ability caused by strength training is due to the different mechanisms responsible for the control of voluntary movements in the dominant and non-dominant lower limb.

Mixing ReaxFF Parameters for Transition Metal Oxides Using Force-Matching Method.

We present the development of the method for the refitting the ReaxFF parameters for a system consisting of the mixed transition metal oxides. We have tested several methods allowing to calculate the differences between the vectors of the forces acting on atoms obtained from the reference DFT simulation and the parameters-dependent ReaxFF. We conclude that the footrule method yields the best parameters among the investigated options. We then validate the parameters using the system consisting of the hematite supported (TiO2)n clusters. The results indicate the refitted parameters allow to obtain much better geometries of the clusters upon MD simulation on the ReaxFF level, and despite the short timescale lead to the stable structures.

Beyond the Scales: A physics-informed machine learning approach for more efficient modeling of SARS-CoV-2 spike glycoprotein

This paper presents a physics-informed machine learning approach to the derivation of a bottom-up coarse-grained model of the SARS-CoV-2 spike glycoprotein from all-atomic molecular dynamics simulations. The machine learning procedure employs a force-matching scheme in the optimization of interaction parameters, where the force-matching scheme is combined in methodology with the initialization of the interaction parameters by the traditional iterative Boltzmann inversion method. The force-matched machine learning procedure is constructed based on two physics-informed layers: one is the Harmonic layer consisting of bond, angle, and dihedral terms as bonded potentials; the other is the Lennard-Jones layer consisting of the non-bonded Lennard-Jones potential. Coarse-grained validation simulations are performed with the learned parameters to test the derived bottom-up coarse-grained model. The simulations are able to reach the microsecond time scale with stability. The physics-informed learning approach yields simulation speeds nearly 40,000 times faster than conventional all-atomic simulations while maintaining comparable simulation accuracy. Additionally, through examination of the non-bonded Lennard-Jones parameters and the radial distribution function analysis, the learning approach matches pairwise distances of the ground-truth data with greater accuracy than the conventional iterative approach method.

Inter-Personal Motor Synergy: Co-working Strategy Depends on Task Constraints

We investigated the role of task constraints on inter-personal interactions. Twenty-one pairs of co-workers performed a finger force production task on force sensors placed at two ends of a seesaw-like apparatus and matched a combined target force of 20N for 23 seconds over ten trials. There were two experimental conditions: 1) FIXED: the seesaw apparatus was mechanically held in place so that the only task constraint was to match the 20N resultant force, and 2) MOVING: the lever in the apparatus was allowed to rotate freely around its fulcrum, acting like a seesaw, so an additional task constraint to (implicitly) balance the resultant moment was added. We hypothesized that the additional task constraint of moment stabilization imposed on the MOVING condition would deteriorate task performance compared to the FIXED condition; however, this was rejected as the performance of the force matching task was similar between two conditions. We also hypothesized that the central nervous systems (CNSs) would employ distinct co-working strategies or inter-personal motor synergy (IPMS) between conditions to satisfy different task constraints, which was supported by our results. Negative covariance between co-worker's forces in the FIXED condition suggested a force stabilization strategy, while positive covariance in the MOVING condition suggested a moment stabilization strategy, implying that independent CNSs adopt distinct IPMSs depending on task constraints. We speculate that, in the absence of a central neural controller, shared visual and mechanical connections between co-workers may suffice to trigger modulations in the cerebellum of each CNS to satisfy competing task constraints.

Cancer survivors post-chemotherapy exhibit unique proprioceptive deficits in proximal limbs

Background: Oxaliplatin (OX) chemotherapy for colorectal cancer is associated with adverse neurotoxic effects that can contribute to long-term sensorimotor impairments in cancer survivors. It is often thought that the sensorimotor impairments are dominated by OX-induced sensory neuropathy that primarily affects the distal regions of the limb. Recent preclinical studies have identified encoding dysfunction of muscle proprioceptors as an alternative mechanism. Unlike the sensory neuropathy affecting distal limbs, dysfunction of muscle proprioceptors could have more widespread effects. Most investigations of chemotherapy-induced sensorimotor impairments have considered only the effects of distal changes in sensory processing; none have evaluated proximal changes or their influence on function. Our study fills this gap by evaluating the functional use of proprioception in the shoulder and elbow joints of cancer survivors post OX chemotherapy. Methods: We implemented three multidirectional sensorimotor tasks: force matching, target reaching, and postural stability tasks to evaluate various aspects of proprioception and their use. Force and kinematic data of the sensorimotor tasks were collected in 13 cancer survivors treated with OX and 13 age-matched healthy controls. Results: Cancer survivors exhibited less accuracy and precision than an age-matched control group when they had to rely only on proprioceptive information to match force, even for forces that required only torques about the shoulder. There were also small differences in the ability to maintain arm posture but no significant differences in reaching. The force deficits in cancer survivors were significantly correlated with self-reported motor dysfunction. Conclusions: These results suggest that cancer survivors post OX chemotherapy exhibit proximal proprioceptive deficits, and that the deficits in producing accurate and precise forces are larger than those for producing unloaded movements. Current clinical assessments of chemotherapy-related sensorimotor dysfunction are largely limited to distal symptoms. Our study suggests that we also need to consider changes in proximal function. Force matching tasks similar to those used here could provide a clinically meaningful approach to quantifying OX-related movement dysfunction during and after chemotherapy.