Protein docking by Rotation-Based Uniform Sampling (RotBUS) with fast computing of intermolecular contact distance and residue desolvation

<p>Abstract</p> <p>Background</p> <p>Protein-protein interactions are fundamental for the majority of cellular processes and their study is of enormous biotechnological and therapeutic interest. In recent years, a variety of computational approaches to the protein-protein docking problem have been reported, with encouraging results. Most of the currently available protein-protein docking algorithms are composed of two clearly defined parts: the sampling of the rotational and translational space of the interacting molecules, and the scoring and clustering of the resulting orientations. Although this kind of strategy has shown some of the most successful results in the CAPRI blind test <url>http://www.ebi.ac.uk/msd-srv/capri</url>, more efforts need to be applied. Thus, the sampling protocol should generate a pool of conformations that include a sufficient number of near-native ones, while the scoring function should discriminate between near-native and non-near-native proposed conformations. On the other hand, protocols to efficiently include full flexibility on the protein structures are increasingly needed.</p> <p>Results</p> <p>In these work we present new computational tools for protein-protein docking. We describe here the RotBUS (Rotation-Based Uniform Sampling) method to generate uniformly distributed sets of rigid-body docking poses, with a new fast calculation of the optimal contacting distance between molecules. We have tested the method on a standard benchmark of unbound structures and we can find near-native solutions in 100% of the cases. After applying a new fast filtering scheme based on residue-based desolvation, in combination with FTDock plus pyDock scoring, near-native solutions are found with rank ≤ 50 in 39% of the cases. Knowledge-based experimental restraints can be easily included to reduce computational times during sampling and improve success rates, and the method can be extended in the future to include flexibility of the side-chains.</p> <p>Conclusions</p> <p>This new sampling algorithm has the advantage of its high speed achieved by fast computing of the intermolecular distance based on a coarse representation of the interacting surfaces. In addition, a fast desolvation scoring permits the screening of millions of conformations at low computational cost, without compromising accuracy. The protocol presented here can be used as a framework to include restraints, flexibility and ensemble docking approaches.</p

User comfort and naturalness of automated driving: The effect of vehicle kinematics and proxemics on subjective response

Higher-level Automated Vehicles (AVs, SAE Level 4+) need to provide a comfortable user experience to enhance public acceptance. AV driving styles, characterised by vehicle kinematics and proxemics, affect user comfort, with “human-like” driving styles expected to provide natural feelings to further improve user comfort. This study investigated how the kinematic and proxemic characteristics of an AV’s driving style affect user comfort and naturalness of a ride. The similarities in automated and users’ own manual driving style, and how these similarities affect evaluations, was also investigated. Using a motion-based driving simulator, participants experienced three Level 4 automated driving styles (Defensive, Aggressive, and Machine-Learning based), and a manual drive. Participants provided ratings (separately) for comfort and naturalness of each automated controller, as it negotiated twenty-four UK road sections, with varying geometric and roadside features. Linear mixed-effects models were used to examine the effect of kinematics and proxemics of the AV’s driving style, on subjective evaluation of comfort and naturalness of the ride, and how similarities between users’ own driving style and that of the AV affected riders’ evaluation. Results showed that the AV controllers’ lateral and rotational kinematics significantly influenced both comfort and naturalness, while longitudinal jerk only affected comfort. The Euclidean distance in a range of kinematics, characterising similarities between manual and automated driving styles, had varied effects on subjective evaluations. This research facilitates understanding how control features of AVs affect user experience, which will contribute to designing more user-centred controllers, leading to better acceptance of higher-level AVs

Interpreting pedestrians' head movements when encountering automated vehicles at a virtual crossroad

In the future, Automated Vehicles (AVs) may be able to use pedestrians’ head movement patterns to understand their crossing intentions. This ability of the AV to predict pedestrian crossing intention will improve road safety in mixed traffic situations and may also enhance traffic flow, allowing the vehicle to gradually reduce its speed in advance of a yield, eliminating the need for a complete and erratic halt. To date, most of the work conducted on studying pedestrian head movements has been based on observation studies. To further our understanding in this area, this study examined pedestrians’ head movements when interacting with AVs during a range of road crossing scenarios, developed in a VR environment. Thirty-eight participants took part in this CAVE-based pedestrian simulator study. Head movements were recorded using stereoscopic motion-tracking glasses, as pedestrians crossed the road in response to an AV which approached from the right (UK-based road). A zebra crossing was included in half of the trials to understand how it affected crossing behaviour. The effect of different approaching speeds of the AV, and the presence of an external Human-Machine Interface (eHMI), on head movements and crossing behaviour was also studied. Results showed that the absolute head-turning rate (change in pe- destrians’ head-turning angle, per frame) increased significantly at around 1 s before a crossing initiation, reaching a peak at the crossing initiation, where pedestrians presented a “last-second check” before the crossing decision. Another increase in absolute head-turning rate to the right was seen at the end of the crossing (~1.5 s after crossing initiation), to check the proximity of the approaching vehicle. A higher rate of head-turning was also seen for AV-non-yielding scenarios. Finally, the least number of head turns was seen for the yielding conditions which included an eHMI, in the presence of the zebra crossing. These results show the value of infrastructural and vehicle-based cues in assisting pedestrians’ crossing decisions and provide an insight into how head-turning behaviour can be used by AVs to better predict pedestrians’ crossing intentions in urban settings

Effect of Environmental Factors and Individual Differences on Subjective Evaluation of Human-like and Conventional Automated Vehicle Controllers

Achieving optimal performance in human-machine systems, such as highly automated vehicles, relies, in part, on individuals’ acceptance and use of the system, which is in turn affected by their enjoyment of engaging with, or experiencing, the system. This driving simulator study investigated individuals’ real-time subjective evaluation of four different Automated Vehicle (AV) driving styles, in different environmental contexts. Twenty-four participants were recruited to manually drive a contextually rich simulator environment, and to experience human-like and non-human-like AV driving styles, as well as the automated replay of their own manual drive. Their subjective real-time feedback towards these driving styles was analyzed. Our results showed that participants gave higher positive feedback towards the replay of their own drive, compared to the other three controllers. This difference was statistically significant, when compared to the high-speed controller (named as Fast), particularly for sharp curves. With respect to the replay of their own drive, participants gave higher negative feedback when navigating an Urban environment, compared to Rural settings. Moreover, changes in roadside furniture affected individuals’ feedback, and this effect was more prominent when the vehicle was driving closer to the edge of the road. Based on our results, we conclude that individuals’ perception of different AV driving styles changes based on different environmental conditions, including, but not limited to, road geometry and roadside furniture. These findings suggest that humans prefer a slower human-like driving style for AV controllers that adapts its speed and lateral offset to roadside objects and furniture. Investigating individual differences in AV driving style preference showed that low Sensation Seeking individuals preferred the slower human-like controller more than the faster human-like controller. Consideration of this human-centered feedback is important for the design of future AV controllers, to enhance individuals’ ride experience, and potentially improve acceptance and use of these vehicles

Effect of environmental factors and individual differences on subjective evaluation of human-like and conventional automated vehicle controllers

Achieving optimal performance in human-machine systems, such as highly automated vehicles, relies, in part, on individuals’ acceptance and use of the system, which is in turn affected by their enjoyment of engaging with, or experiencing, the system. This driving simulator study investigated individuals’ real-time subjective evaluation of four different Automated Vehicle (AV) driving styles, in different environmental contexts. Twenty-four participants were recruited to manually drive a contextually rich simulator environment, and to experience human-like and non-human-like AV driving styles, as well as the automated replay of their own manual drive. Their subjective real-time feedback towards these driving styles was analyzed. Our results showed that participants gave higher positive feedback towards the replay of their own drive, compared to the other three controllers. This difference was statistically significant, when compared to the high-speed controller (named as Fast), particularly for sharp curves. With respect to the replay of their own drive, participants gave higher negative feedback when navigating an Urban environment, compared to Rural settings. Moreover, changes in roadside furniture affected individuals’ feedback, and this effect was more prominent when the vehicle was driving closer to the edge of the road. Based on our results, we conclude that individuals’ perception of different AV driving styles changes based on different environmental conditions, including, but not limited to, road geometry and roadside furniture. These findings suggest that humans prefer a slower human-like driving style for AV controllers that adapts its speed and lateral offset to roadside objects and furniture. Investigating individual differences in AV driving style preference showed that low Sensation Seeking individuals preferred the slower human-like controller more than the faster human-like controller. Consideration of this human-centered feedback is important for the design of future AV controllers, to enhance individuals’ ride experience, and potentially improve acceptance and use of these vehicles

Will pedestrians cross the road before an Automated Vehicle? The Effect of Drivers' Attentiveness and Presence on Pedestrians' Road Crossing Behavior

The impact of automated vehicles (AV) on pedestrians’ crossing behavior has been the topic of some recent studies, but findings are still scarce and inconclusive. The aim of this study is to determine whether the drivers’ presence and apparent attentiveness in a vehicle influences pedestrians’ crossing behavior, perceived behavioral control, and perceived risk, in a controlled environment, using a Head-mounted Display in an immersive Virtual Reality study. Twenty participants took part in a road-crossing experiment. The VR environment consisted of a single lane one-way road with car traffic approaching from the right-hand side of the participant which travelled at 30 kmph. Participants were asked to cross the road if they felt safe to do so. The effect of three driver conditions on pedestrians’ crossing behavior were studied: Attentive driver, distracted driver, and no driver present. Two vehicles were employed with a fixed time gap (3.5 s and 5.5s) between them to study the effects of time gaps on pedestrians’ crossing behavior. The manipulated vehicle yielded to the pedestrians in half of the trials, stopping completely before reaching the pedestrian’s position. The crossing decision, time to initiate the crossing, crossing duration, and safety margin were measured. The main findings show that the vehicle’s motion cues (i.e. the gap between the vehicles, and the yielding behavior of the vehicle) were the most important factors affecting pedestrians’ crossing behavior. Therefore, future research should focus more on investigating how AVs should behave while interacting with pedestrians. Distracted driver condition leads to shorter crossing initiation time but the effect was small. No driver condition leads to smaller safety margin. Findings also showed that perceived behavioral control was higher and perceived risk was significantly lower when the driver appeared attentive. Given that drivers will be allowed to do other tasks while AVs are operating in the future, whether explicit communication will be needed in this situation should be further investigated

Drivers’ Evaluation of Different Automated Driving Styles: Is It both Comfortable and Natural?

Objective: This study investigated users’ subjective evaluation of three highly automated driving styles, in terms of comfort and naturalness, when negotiating a UK road in a high-fidelity, motion-based, driving simulator. Background: Comfort and naturalness are thought to play an important role in contributing to users’ acceptance and trust of automated vehicles (AVs), although not much is understood about the types of driving style which are considered comfortable or natural. Method: A driving simulator study, simulating roads with different road geometries and speed limits, was conducted. Twenty-four participants experienced three highly automated driving styles, two of which were recordings from human drivers, and the other was based on a machine learning (ML) algorithm, termed Defensive, Aggressive, and Turner respectively. Participants evaluated comfort or naturalness of each driving style, for each road segment, and completed a Sensation Seeking (SS) questionnaire, which assessed their risk-taking propensity. Results: Participants regarded human-like driving styles as more comfortable and natural, compared with the less human-like, ML-based, driving controller. However, between the two human-like controllers, only the Defensive style was considered comfortable, especially for the more challenging road environments. Differences in preference for controller by driver trait were also observed, with the Aggressive driving style evaluated as more natural by the high sensation seekers. Conclusion: Participants were able to distinguish between human- and machine-like AV controllers. A range of psychological concepts must be considered for the subjective evaluation of controllers. Application: Knowing how different driver groups evaluate automated vehicle controllers is important to design more acceptable systems in the future

Who goes first? A distributed simulator study of vehicle-pedestrian interaction

One of the current challenges of automation is to have highly automated vehicles (HAVs) that communicate effectively with pedestrians and react to changes in pedestrian behaviour, to promote more trustable HAVs. However, the details of how human drivers and pedestrians interact at unsignalised crossings remain poorly understood. We addressed some aspects of this challenge by replicating vehicle-pedestrian interactions in a safe and controlled virtual environment by connecting a high fidelity motion-based driving simulator to a CAVE-based pedestrian lab in which 64 participants (32 pairs of one driver and one pedestrian) interacted with each other under different scenarios. The controlled setting helped us study the causal role of kinematics and priority rules on interaction outcome and behaviour, something that is not possible in naturalistic studies. We also found that kinematic cues played a stronger role than psychological traits like sensation seeking and social value orientation in determining whether the pedestrian or driver passed first at unmarked crossings. One main contribution of this study is our experimental paradigm, which permitted repeated observation of crossing interactions by each driver-pedestrian participant pair, yielding behaviours which were qualitatively in line with observations from naturalistic studies

Study of the flexibility of GroEL through FFEA simulation and analysis

Input scripts, structural information and output trajectory, measurement and analysis data of GroEL using FFEA supporting the results presented in the article "Fluctuating Finite Element Analysis (FFEA): A Continuum Mechanics Software Tool for Mesoscale Simulation of Biomolecules" in PLoS Computational Biolog