Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups-a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs.Monte Carlo | polyampholyte | polyelectrolyte I ntrinsically disordered proteins (IDPs) are a class of proteins that fail to fold autonomously in aqueous solutions to welldefined three-dimensional structures (1, 2). This "intrinsic disorder" has been implicated in a range of regulatory functions that require IDPs to interact with other macromolecular ligands (3-11). Many of these interactions promote disorder-to-order transitions within IDPs (3, 9), and different mechanistic models (3, 12, 13) have been proposed for coupled folding and binding. To develop a better understanding of how disorder is used in function (2), we have pursued quantitative, polymer-physics-based descriptions (14-16) for conformational ensembles of .Low hydrophobicity is a defining characteristic of IDP sequences (21,22). This suggests that IDPs cannot collapse to form compact, globular conformations in aqueous solutions (21). However, spectroscopic (23-27) and computational investigations (17, 28) have shown that polar tracts form heterogeneous ensembles of collapsed structures in aqueous solutions. These sequences are rich in uncharged, polar amino acids and are devoid of canonical hydrophobic residues. Collapse of polar tracts has been observed for polyglutamine (17...

Common goals in the development of human-machine interface (HMI) technology are to reduce cognitive workload and increase function. However, objective and quantitative outcome measures assessing cognitive workload have not been standardized for HMI research. The present study examines the efficacy of a simple event-related potential (ERP) measure of cortical effort during myoelectric control of a virtual limb for use as an outcome tool. Participants trained and tested on two methods of control, direct control (DC) and pattern recognition control (PRC), while electroencephalographic (EEG) activity was recorded. Eighteen healthy participants with intact limbs were tested using DC and PRC under three conditions: passive viewing, easy, and hard. Novel auditory probes were presented at random intervals during testing, and significant task-difficulty effects were observed in the P200, P300, and a late positive potential (LPP), supporting the efficacy of ERPs as a cognitive workload measure in HMI tasks. LPP amplitude distinguished DC from PRC in the hard condition with higher amplitude in PRC, consistent with lower cognitive workload in PRC relative to DC for complex movements. Participants completed trials faster in the easy condition using DC relative to PRC, but completed trials more slowly using DC relative to PRC in the hard condition. The results provide promising support for ERPs as an outcome measure for cognitive workload in HMI research such as prosthetics, exoskeletons, and other assistive devices, and can be used to evaluate and guide new technologies for more intuitive HMI control.

Pattern recognition can provide intuitive control of myoelectric prostheses. Currently, screen-guided training (SGT), in which individuals perform specific muscle contractions in sync with prompts displayed on a screen, is the common method of collecting the electromyography (EMG) data necessary to train a pattern recognition classifier. Prosthesis-guided training (PGT) is a new data collection method that requires no additional hardware and allows the individuals to keep their focus on the prosthesis itself. The movement of the prosthesis provides the cues of when to perform the muscle contractions. This study compared the training data obtained from SGT and PGT and evaluated user performance after training pattern recognition classifiers with each method. Although the inclusion of transient EMG signal in PGT data led to decreased accuracy of the classifier, subjects completed a performance task faster than when compared to using a classifier built from SGT data. This may indicate that training data collected using PGT that includes both steady state and transient EMG signals generates a classifier that more accurately reflects muscle activity during real-time use of a pattern recognition-controlled myoelectric prosthesis.

No abstract