Human Hopping Research Articles

Role of compliant mechanics and motor control in hopping - from human to robot

Compliant leg function found during bouncy gaits in humans and animals can be considered a role model for designing and controlling bioinspired robots and assistive devices. The human musculoskeletal design and control differ from distal to proximal joints in the leg. The specific mechanical properties of different leg parts could simplify motor control, e.g., by taking advantage of passive body dynamics. This control embodiment is complemented by neural reflex circuitries shaping human motor control. This study investigates the contribution of specific passive and active properties at different leg joint levels in human hopping at different hopping frequencies. We analyze the kinematics and kinetics of human leg joints to design and control a bioinspired hopping robot. In addition, this robot is used as a test rig to validate the identified concepts from human hopping. We found that the more distal the joint, the higher the possibility of benefit from passive compliant leg structures. A passive elastic element nicely describes the ankle joint function. In contrast, a more significant contribution to energy management using an active element (e.g., by feedback control) is predicted for the knee and hip joints. The ankle and knee joints are the key contributors to adjusting hopping frequency. Humans can speed up hopping by increasing ankle stiffness and tuning corresponding knee control parameters. We found that the force-modulated compliance (FMC) as an abstract reflex-based control beside a fixed spring can predict human knee torque-angle patterns at different frequencies. These developed bioinspired models for ankle and knee joints were applied to design and control the EPA-hopper-II robot. The experimental results support our biomechanical findings while indicating potential robot improvements. Based on the proposed model and the robot’s experimental results, passive compliant elements (e.g. tendons) have a larger capacity to contribute to the distal joint function compared to proximal joints. With the use of more compliant elements in the distal joint, a larger contribution to managing energy changes is observed in the upper joints.

Validation of a musculoskeletal model for simulating muscle mechanics and energetics during diverse human hopping tasks.

Computational musculoskeletal modelling has emerged as an alternative, less-constrained technique to indirect calorimetry for estimating energy expenditure. However, predictions from modelling tools depend on many assumptions around muscle architecture and function and motor control. Therefore, these tools need to continue to be validated if we are to eventually develop subject-specific simulations that can accurately and reliably model rates of energy consumption for any given task. In this study, we used OpenSim software and experimental motion capture data to simulate muscle activations, muscle fascicle dynamics and whole-body metabolic power across mechanically and energetically disparate hopping tasks, and then evaluated these outputs at a group- and individual-level against experimental electromyography, ultrasound and indirect calorimetry data. Comparing simulated and experimental outcomes, we found weak to strong correlations for peak muscle activations, moderate to strong correlations for absolute fascicle shortening and mean shortening velocity, and strong correlations for gross metabolic power. These correlations tended to be stronger on a group-level rather than individual-level. We encourage the community to use our publicly available dataset from SimTK.org to experiment with different musculoskeletal models, muscle models, metabolic cost models, optimal control policies, modelling tools and algorithms, data filtering etc. with subject-specific simulations being a focal goal.

Linking muscle mechanics to the metabolic cost of human hopping.

Many models have been developed to predict metabolic energy expenditure based on biomechanical proxies of muscle function. However, current models may only perform well for select forms of locomotion, not only because the models are rarely rigorously tested across subtle and broad changes in locomotor task but also because previous research has not adequately characterised different forms of locomotion to account for the potential variability in muscle function and thus metabolic energy expenditure. To help to address the latter point, the present study imposed frequency and height constraints to hopping and quantified gross metabolic power as well as the activation requirements of medial gastrocnemius (MG), lateral gastrocnemius (GL), soleus (SOL), tibialis anterior (TA), vastus lateralis (VL), rectus femoris (RF) and biceps femoris (BF), and the work requirements of GL, SOL and VL. Gross metabolic power increased with a decrease in hop frequency and increase in hop height. There was no hop frequency or hop height effect on the mean electromyography (EMG) data of ankle musculature; however, the mean EMG of VL and RF increased with a decrease in hop frequency and that of BF increased with an increase in hop height. With a reduction in hop frequency, GL, SOL and VL fascicle shortening, fascicle shortening velocity and fascicle to MTU shortening ratio increased, whereas with an increase in hop height, only SOL fascicle shortening velocity increased. Therefore, within the constraints that we imposed, decreases in hop frequency and increases in hop height resulted in increases in metabolic power that could be explained by increases in the activation requirements of knee musculature and/or increases in the work requirements of both knee and ankle musculature.

Exploring the effects of serial and parallel elasticity on a hopping robot.

The interaction between the motor control and the morphological design of the human leg is critical for generating efficient and robust locomotion. In this paper, we focus on exploring the effects of the serial and parallel elasticity on hopping with a two-segmented robotic leg called electric-pneumatic actuation (EPA)-Hopper. EPA-Hopper uses a hybrid actuation system that combines electric motors and pneumatic artificial muscles (PAM). It provides direct access to adjust the physical compliance of the actuation system by tuning PAM pressures. We evaluate the role of the serial and parallel PAMs with different levels of compliance with respect to four criteria: efficiency, performance, stability, and robustness of hopping against perturbations. The results show that the serial PAM has a more pronounced impact than the parallel PAM on these criteria. Increasing the stiffness of the serial PAM decreases the leg stiffness of the unloading phase during hopping. The stiffer the leg, the more efficient and the less robust the movement. These findings can help us further understand the human hopping mechanism and support the design and control of legged robots and assistive devices.

Bioinspired Legged Robot Design via Blended Physical and Virtual Impedance Control

In order to approach the performance of biological locomotion in legged robots, better integration between body design and control is required. In that respect, understanding the mechanics and control of human locomotion will help us build legged robots with comparable efficient performance. From another perspective, developing bioinspired robots can also improve our understanding of human locomotion. In this work, we create a bioinspired robot with a blended physical and virtual impedance control to configure the robot’s mechatronic setup. We consider human neural control and musculoskeletal system a blueprint for a hopping robot. The hybrid electric-pneumatic actuator (EPA) presents an artificial copy of this biological system to implement the blended control. By defining efficacy as a metric that encompasses both performance and efficiency, we demonstrate that incorporating a simple force-based control besides constant pressure pneumatic artificial muscles (PAM) alone can increase the efficiency up to 21% in simulations and 7% in experiments with the 2-segmented EPA-hopper robot. Also, we show that with proper adjustment of the force-based controller and the PAMs, efficacy can be further increased to 41%. Finally, experimental results with the 3-segmented EPA-hopper robot and comparisons with human hopping confirm the extendability of the proposed methods to more complex robots.

Series elasticity facilitates safe plantar flexor muscle-tendon shock absorption during perturbed human hopping.

In our everyday lives, we negotiate complex and unpredictable environments. Yet, much of our knowledge regarding locomotion has come from studies conducted under steady-state conditions. We have previously shown that humans rely on the ankle joint to absorb energy and recover from perturbations; however, the muscle-tendon unit (MTU) behaviour and motor control strategies that accompany these joint-level responses are not yet understood. In this study, we determined how neuromuscular control and plantar flexor MTU dynamics are modulated to maintain stability during unexpected vertical perturbations. Participants performed steady-state hopping and, at an unknown time, we elicited an unexpected perturbation via rapid removal of a platform. In addition to kinematics and kinetics, we measured gastrocnemius and soleus muscle activations using electromyography and in vivo fascicle dynamics using B-mode ultrasound. Here, we show that an unexpected drop in ground height introduces an automatic phase shift in the timing of plantar flexor muscle activity relative to MTU length changes. This altered timing initiates a cascade of responses including increased MTU and fascicle length changes and increased muscle forces which, when taken together, enables the plantar flexors to effectively dissipate energy. Our results also show another mechanism, whereby increased co-activation of the plantar- and dorsiflexors enables shortening of the plantar flexor fascicles prior to ground contact. This co-activation improves the capacity of the plantar flexors to rapidly absorb energy upon ground contact, and may also aid in the avoidance of potentially damaging muscle strains. Our study provides novel insight into how humans alter their neural control to modulate in vivo muscle-tendon interaction dynamics in response to unexpected perturbations. These data provide essential insight to help guide design of lower-limb assistive devices that can perform within varied and unpredictable environments.

Hopping frequency influences elastic energy reuse with joint series elastic actuators

Robotic limb design struggles to combine energy efficiency with human-like levels of movement versatility. High efficiency and a range of angles and torques are characteristics of human hopping at different frequencies. Humans use muscles in combination with tendons to achieve the required joint actuation. Therefore, we consider whether appropriately tuned series elastic actuators (SEAs) placed at the leg joints can be used to reduce the functional gap between robots and humans. Human hip, knee, and ankle biomechanics were recorded over a range of hopping frequencies to extract joint angles and torques, which were used as an input to a mechanical simulation SEA model. This model was used to optimize the SEA stiffness of each joint to either minimize peak power or energy requirements. This work investigated the relationship between hopping frequency and SEA stiffness, the utility of using SEAs at each joint, and the reasons behind humans’ preferred hopping frequency. Although the constant stiffness values across different hopping frequencies are suitable for the knee and the ankle, a variable serial elastic actuator stiffness could still further reduce energy requirements. Optimal SEA stiffness was found to reduce peak power requirements by up to 73% at the ankle and up to 66% at the knee, with greatest benefits found around the preferred frequency. However, no SEA benefits were found for the hip and above the preferred hopping frequency for the knee. These insights could be used to aid in the design of robotic and assistive devices to achieve versatile and energy efficient human-like movements.

Regulation of foot and ankle quasi-stiffness during human hopping across a range of frequencies

Human legs operate like springs with adjustable stiffness during locomotion, improving movement economy and versatility. The potential for the foot to contribute to this spring-like mechanism has been established. However, due to previous modelling approaches assuming a rigid-foot segment, it is unknown if ankle and foot quasi-stiffness can be actively regulated, quasi-stiffness being a measure of joint deformation under an applied load. In this study, we sought to determine if midfoot quasi-stiffness was increased in a similar manner as the ankle with increasing load demands, and if these changes were mediated by increased activation of the intrinsic foot muscles. We also quantified differences in measures of ankle joint quasi-stiffness attributable to the modelling assumption of a rigid-foot segment versus a multi-segment foot. Twenty-two healthy individuals performed a single-leg hopping task at three frequencies (2.0 Hz, 2.3 Hz, and 2.6 Hz) while measuring lower limb kinematics, kinetics and muscle activation (EMG). Kinetics and kinematics were calculated at the midfoot and using two different ankle models: rigid-foot model (shank-foot) and an anatomical ankle (shank-calcaneus). Midfoot quasi-stiffness increased with hopping-frequency (p < 0.05), while contact phase intrinsic foot muscle activation decreased (p < 0.05). The assumption of a rigid-foot model overestimated ankle ROM by ~10° and underestimated ankle quasi-stiffness by 45–60%. This study demonstrates that midfoot quasi-stiffness increases with hopping-frequency; however, the mechanism for these changes remains unclear. Furthermore, this study demonstrates the need to assess the ankle and foot independently, using appropriate models, to avoid significant inaccuracies in basic ankle kinematic and kinetic outputs, such as range of motion and joint quasi-stiffness.

Correction to 'Humans falling in holes: adaptations in lower-limb joint mechanics in response to a rapid change in substrate height during human hopping'.

In getting from here to there, we continuously negotiate complex environments and unpredictable terrain. Our ability to stay upright in the face of obstacles, such as holes in the ground, is quite remarkable. However, we understand relatively little about how humans adjust limb mechanical behaviour to recover from unexpected perturbations. In this study, we determined how the joints of the lower-limb respond to recover from a rapid, unexpected drop in substrate height during human hopping. We recorded lower-limb kinematics and kinetics while subjects performed steady-state hopping at their preferred frequency on an elevated platform (5, 10 and 20 cm). At an unknown time, we elicited an unexpected perturbation (i.e. a hole in the ground) via the rapid removal of the platform. Based on previous research in bipedal birds, we hypothesized (i) that distal joints would play an increased role in fall recovery when compared to steady-state hopping, and (ii) that patterns of joint power redistribution would be more pronounced with increases in perturbation height. Our results suggest that humans successfully recover from falling in a hole by increasing the energy absorbed predominantly in distal lower-limb joints (i.e. the ankle) across perturbation heights ranging from 5 to 10 cm. However, with increased perturbation height (20 cm) humans increase their reliance on the more proximal lower-limb joints (i.e. the knee and the hip) to absorb mechanical energy and stabilize fall recovery. Further investigations into the muscle-tendon mechanics underlying these joint-level responses will likely provide additional insights into the neuromotor control strategies used to regain the stability following unexpected perturbations and provide biological inspiration for the future design of wearable devices capable of performing within unpredictable environments.

Hopping with degressive spring stiffness in a full-leg exoskeleton lowers metabolic cost compared with progressive spring stiffness and hopping without assistance.

When humans hop with a passive-elastic exoskeleton with springs in parallel with both legs, net metabolic power (Pmet) decreases compared with normal hopping (NH). Furthermore, humans retain near-constant total vertical stiffness (ktot) when hopping with such an exoskeleton. To determine how spring stiffness profile affects Pmet and biomechanics, 10 subjects hopped on both legs normally and with three full-leg exoskeletons that each used a different spring stiffness profile at 2.4, 2.6, 2.8, and 3.0 Hz. Each subject hopped with an exoskeleton that had a degressive spring stiffness (DGexo), where stiffness, the slope of force vs. displacement, is initially high but decreases with greater displacement, linear spring stiffness (LNexo), where stiffness is constant, or progressive spring stiffness (PGexo), where stiffness is initially low but increases with greater displacement. Compared with NH, use of the DGexo, LNexo, and PGexo numerically resulted in 13-24% lower, 4-12% lower, and 0-8% higher Pmet, respectively, at 2.4-3.0 Hz. Hopping with the DGexo reduced Pmet compared with NH at 2.4-2.6 Hz (P ≤ 0.0457) and reduced Pmet compared with the PGexo at 2.4-2.8 Hz (P < 0.001). ktot while hopping with each exoskeleton was not different compared with NH, suggesting that humans adjust leg stiffness to maintain overall stiffness regardless of the spring stiffness profile in an exoskeleton. Furthermore, the DGexo provided the greatest elastic energy return, followed by LNexo and PGexo (P ≤ 0.001). Future full-leg, passive-elastic exoskeleton designs for hopping, and presumably running, should use a DGexo rather than an LNexo or a PGexo to minimize metabolic demand.NEW & NOTEWORTHY When humans hop at 2.4-3.0 Hz normally and with an exoskeleton with different spring stiffness profiles in parallel to the legs, net metabolic power is lowest when hopping with an exoskeleton with degressive spring stiffness. Total vertical stiffness is constant when using an exoskeleton with linear or nonlinear spring stiffness compared with normal hopping. In-parallel spring stiffness influences net metabolic power and biomechanics and should be considered when designing passive-elastic exoskeletons for hopping and running.

CORRIGENDUM.

CorrigendumCORRIGENDUMPublished Online:18 Apr 2019https://doi.org/10.1152/japplphysiol.zdg-3016-corr.2019Original articleMoreSectionsPDF (31 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Grabowski AM, Herr HM. Leg exoskeleton reduces the metabolic cost of human hopping. J Appl Physiol 107: 670–678, 2009. First published May 7, 2009; doi:10.1152/japplphysiol.91609.2008.—In Table 2, standard deviations for kdim and dhops were incorrect. The corrected table appears below.Table 2. kdim and kinematics of hopping with and without a leg exoskeletonSessionHopping Frequency, Hzkdimtc, shvert, cmdhops, cmNormal2.01 ± 0.0116.80 ± 1.600.379 ± 0.0271.14 ± 0.614.32 ± 2.02MLE2.02 ± 0.0117.87 ± 2.760.358 ± 0.0411.78 ± 1.406.40 ± 3.35†SLE2.01 ± 0.0116.40 ± 1.48*0.383 ± 0.0241.43 ± 0.603.60 ± 2.01*Normal2.20 ± 0.0220.70 ± 1.280.340 ± 0.0230.98 ± 0.374.07 ± 2.57MLE2.21 ± 0.0220.51 ± 1.900.339 ± 0.0251.36 ± 0.675.64 ± 3.02†SLE2.21 ± 0.0220.48 ± 2.36†0.346 ± 0.0241.12 ± 0.383.85 ± 1.87*Normal2.41 ± 0.0125.58 ± 1.780.314 ± 0.0190.60 ± 0.254.68 ± 2.20MLE2.41 ± 0.0224.50 ± 1.870.321 ± 0.0150.81 ± 0.394.12 ± 2.12SLE2.42 ± 0.0124.55 ± 1.780.321 ± 0.0180.82 ± 0.413.53 ± 1.80Normal2.61 ± 0.0231.07 ± 1.870.286 ± 0.0260.57 ± 0.504.37 ± 2.38MLE2.61 ± 0.0130.33 ± 2.750.289 ± 0.0170.80 ± 0.374.23 ± 2.19SLE2.61 ± 0.0229.13 ± 2.52*0.300 ± 0.014*0.63 ± 0.272.92 ± 1.69*Values are means ± SD. Shown are hopping frequency, dimensionless stiffness (kdim), contact time (tc), hopping height (hvert), and mean distance between consecutive hops (dhops) averaged from 15 hops/subject with and without (normal) wearing a leg exoskeleton (MLE and SLE). kdim equals the ratio of peak ground reaction force (GRF) in units of body weight and peak center of mass displacement normalized by leg length.*Significant difference (P 0.05) between hopping with the MLE and SLE;†significant difference (P 0.05) between hopping with and without (normal) an exoskeleton.This article has no references to display. Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesLeg exoskeleton reduces the metabolic cost of human hopping 01 Sep 2009Journal of Applied Physiology More from this issue > Volume 126Issue 4April 2019Pages 1173-1173 Copyright & PermissionsCopyright © 2019 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.zdg-3016-corr.2019PubMed30998444History Published online 18 April 2019 Published in print 1 April 2019 Metrics

Human-like hopping in machines

Template models of legged locomotion are powerful tools for gait analysis, but can also inspire robot design and control. In this paper, a spring-loaded inverted pendulum (SLIP) model is employed to control vertical hopping of a 2-segmented legged robot. Feed-forward and bio-inspired virtual model control using the SLIP model are compared. In the latter approach, the feedback control emulates a virtual spring between hip and foot. The results demonstrate similarity of human and robot hopping. Moreover, the feedback control proves to simplify and improve hopping control. It yields better perturbation recovery and locomotion adaptation and is even easier to tune. Thus, human-like hopping is achievable using a rather simple template-based controller, which ensures the required performance, robustness and versatility.

Metabolic cost of human hopping.

To interpret the movement strategies employed in locomotion, it is necessary to understand the source of metabolic cost. Muscles must consume metabolic energy to do work, but also must consume energy to generate force. The energy lost during steady locomotion and, hence, the amount of mechanical work muscles need to perform to replace it can be reduced and, in theory, even eliminated by elastically storing and returning some portion of this energy via the tendons. However, even if muscles do not need to perform any mechanical work, they still must generate sufficient force to tension tendons and support body weight. This study shows that the metabolic cost per hop of human hopping can largely be explained by the cost of producing force over the duration of a hop. Metabolic cost determined via oxygen consumption is compared with theoretical predictions made using a number of different cost functions that include terms for average muscle work, force, force rate and impulse (time integral of muscle force). Muscle impulse alone predicts metabolic cost per hop as well as more complex functions that include terms for muscle work, force and force rate, and explains a large portion (92%) of the variation in metabolic cost per hop. This is equivalent to 1/effective mechanical advantage, explaining a large portion (66%) of the variation in metabolic cost per time per unit body weight. This result contrasts with studies that suggest that muscle force rate or muscle force rate per time determines the metabolic cost per time of force production in other bouncing gaits such as running.

Escorted by chaperones: Sti1 helps to usher precursor proteins from the ribosome to mitochondria.

Little is known about factors that interact with mitochondrial precursor proteins in the cytosol. Employing site-specific crosslinking this study identifies chaperones of the Hsp70 and Hsp90 families as well as Sti1 as escorts of cytosolic preproteins. Sti1 presumably helps to hand-over preproteins from Hsp70 to the Hsp90 system and thereby facilitates their binding to TOM receptors on the mitochondrial surface.

ATRIAS: Design and validation of a tether-free 3D-capable spring-mass bipedal robot

ATRIAS is a human-scale 3D-capable bipedal robot designed to mechanically embody the spring-mass model for dynamic walking and running. To help bring the extensive work on this theoretical model further into practice, we present the design and validation of a spring-mass robot that can operate in real-world settings (i.e. off-tether and without planarizing restraints). We outline the mechanisms and design choices necessary to meet these specifications, particularly ATRIAS’ four-bar series-elastic leg design. We experimentally demonstrate the following robot capabilities, which are characteristics of the target model. 1) We present the robot’s physical capability for both grounded and aerial gaits, including planar walking and sustained hopping, while being more efficient than similarly gait-versatile bipeds. 2) The robot can be controlled by enforcing quantities derived from the simpler spring-mass model, such as leg angles and leg forces. 3) ATRIAS replicates the center-of-mass dynamics of human hopping and (novelly) walking, a key spring-mass model feature. Lastly, we present dynamically stable stepping in 3D without external support, demonstrating that this theoretical model has practical potential for real-world locomotion.

The dynamic limits of hop height: Biological actuator capabilities and mechanical requirements of task produce incongruity between one- and two-legged performance.

The maximum hop height attainable for a given hop frequency falls well below the theoretical limit dictated by gravity, h = g/8f(2). However, maximum hop height is proportional to 1/f(2), suggesting that ground reaction force and, hence, force production capabilities of the leg muscles limit human hopping performance. Curiously, during one-legged hopping, subjects were able to produce substantially more than 50% the ground reaction force produced during two-legged maximum height hopping-66% on average and as much as 90% the total force produced during two-legged hopping. This implies that two legs together should be able to produce an average of 1.32 times and as much as 1.8 times the force actually measured during two-legged maximum height hopping. Why were our subjects unable to access this extra force capacity when hopping on two legs? Here, we show that this apparent bilateral deficit and other features of maximum height hopping can be explained by the interaction of the mechanical requirements of hopping with the force-velocity and force-length relationships that dictate the force production capacity of the leg muscles. Identifying the factors that limit performance in hopping provides an opportunity to understand how functional limits are determined in more complex activities such as running and jumping.

Hopping locomotion at different gravity: metabolism and mechanics in humans.

Previous literature on the effects of low gravity on the mechanics and energetics of human locomotion already dealt with walking, running, and skipping. The aim of the present study is to obtain a comprehensive view on that subject by including measurements of human hopping in simulated low gravity, a gait often adopted in many Apollo Missions and documented in NASA footage. Six subjects hopped at different speeds at terrestrial, Martian, and Lunar gravity on a treadmill while oxygen consumption and 3D body kinematic were sampled. Results clearly indicate that hopping is too metabolically expensive to be a sustainable locomotion on Earth but, similarly to skipping (and running), its economy greatly (more than ×10) increases at lower gravity. On the Moon, the metabolic cost of hopping becomes even lower than that of walking, skipping, and running, but the general finding is that gaits with very different economy on Earth share almost the same economy on the Moon. The mechanical reasons for such a decrease in cost are discussed in the paper. The present data, together with previous findings, will allow also to predict the aerobic traverse range/duration of astronauts when getting far from their base station on low gravity planets.

Stretch reflex improves rolling stability during hopping of a decerebrate biped system

When humans hop, attitude recovery can be observed in both the sagittal and frontal planes. While it is agreed that the brain plays an important role in leg placement, the role of low-level feedback (the stretch reflex) on frontal plane stabilization remains unclear. Seeking to better understand the contribution of the soleus stretch reflex to rolling stability, we performed experiments on a biomimetic humanoid hopping robot. Various reflex responses to touching the floor, ranging from no response to long muscle activations, were examined, and the effect of a delay upon touching the floor was also examined. We found that the stretch reflex brought the system closer to stable, straight hopping. The presence of a delay did not affect the results; both the cases with and without a delay outperformed the case without a reflex response. The results of this study highlight the importance of low-level control in locomotion for which body stabilization does not require higher-level signals.

Hop/Sti1 phosphorylation inhibits its co-chaperone function.

In eukaryotes, the molecular chaperones Hsp90 and Hsp70 are connected via the co-chaperone Sti1/Hop, which allows transfer of clients. Here, we show that the basic functions of yeast Sti1 and human Hop are conserved. These include the simultaneous binding of Hsp90 and Hsp70, the inhibition of the ATPase activity of Hsp90, and the ability to support client activation in vivo. Importantly, we reveal that both Hop and Sti1 are subject to inhibitory phosphorylation, although the sites modified and the influence of regulatory phosphorylation is species specific. Phospho-mimetic variants have a reduced ability to activate clients in vivo and different affinity for Hsp70. Hop is more tightly regulated, as phosphorylation affects also the interaction with Hsp90 and induces structural rearrangements in the core part of the protein.

Plasmodium falciparum Hop: Detailed analysis on complex formation with Hsp70 and Hsp90

The heat shock organizing protein (Hop) is important in modulating the activity and co-interaction of two chaperones: heat shock protein 70 and 90 (Hsp70 and Hsp90). Recent research suggested that Plasmodium falciparum Hop (PfHop), PfHsp70 and PfHsp90 form a complex in the trophozoite infective stage. However, there has been little computational research on the malarial Hop protein in complex with other malarial Hsps. Using in silico characterization of the protein, this work showed that individual domains of Hop are evolving at different rates within the protein. Differences between human Hop (HsHop) and PfHop were identified by motif analysis. Homology modeling of PfHop and HsHop in complex with their own cytosolic Hsp90 and Hsp70 C-terminal peptide partners indicated excellent conservation of the Hop concave TPR sites bound to the C-terminal motifs of partner proteins. Further, we analyzed additional binding sites between Hop and Hsp90, and showed, for the first time, that they are distinctly less conserved between human and malaria parasite. These sites are located on the convex surface of Hop TPR2, and involved in interactions with the Hsp90 middle domain. Since the convex sites are less conserved than the concave sites, it makes their potential for malarial inhibitor design extremely attractive (as opposed to the concave sites which have been the focus of previous efforts).