Determination of locked interfaces in biomolecular complexes using Haptimol_RD

Iakovou, Georgios; Laycock, Stephen D.; Hayward, Steven

doi:10.2142/biophysico.13.0_97

Cited by 5 publications

(9 citation statements)

References 33 publications

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“…This drop in interaction energy is accompanied by a strong force on the haptic device that gives the impression that the ligand is being “sucked” into the correct pose with the receptor. A previous study of this effect indicated that whether the correct pose can be achieved with rigid body docking is related to the nature of the interface. Some interfaces are simple and suggest that the molecules are already folded before complex formation (see “Ghostifying” section below), whereas others have an interwinding interface indicating considerable intrasubunit conformational change occurs upon complex formation .…”

Section: Results and Discussionmentioning

confidence: 95%

Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics

Iakovou

Hayward

Laycock

2017

J. Chem. Inf. Model.

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Haptic technology facilitates user interaction with the virtual world via the sense of touch. In molecular docking, haptics enables the user to sense the interaction forces during the docking process. Here we describe a haptics-assisted interactive software tool, called Haptimol RD, for the study of docking interactions. By utilising GPU-accelerated proximity querying methods very large systems can now be studied.Methods for force scaling, multipoint collision response and haptic navigation are described that address force stability issues that are particular to the interactive docking of large systems. Thus Haptimol RD expands, for the first time, the use of interactive biomolecular haptics to the study of protein-protein interactions. Unlike existing approaches, Haptimol RD is designed to run on relatively inexpensive consumer-level hardware and is freely available to the community.

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Section: Results and Discussionmentioning

confidence: 95%

Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics

Iakovou

Hayward

Laycock

2017

J. Chem. Inf. Model.

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“…computes the interaction forces in real time, rather than relying on any precomputation, and as a result, it can be applied to a flexible docking problem. The effectiveness of this approach was demonstrated by Iakovou et al…”

Section: Interactive Dockingmentioning

confidence: 95%

“…Importantly for our docking approach, in which receptor flexibility is modelled, the method by Iakovou et al 48 computes the interaction forces in real time, rather than relying on any pre-computation and, as a result, it can be applied to a flexible docking problem. The effectiveness of this approach was demonstrated in Iakovou et al 49 .…”

Section: Interactive Dockingmentioning

confidence: 96%

Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility

Matthews

Kitao

Laycock

et al. 2019

J. Chem. Inf. Model.

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Haptic-assisted interactive docking tools immerse the user in an environment where intuition and knowledge can be used to help guide the docking process. Here we present such a tool where the user "holds" a rigid ligand via a haptic device through which they feel interaction forces with a flexible receptor biomolecule. To ensure forces transmitted through the haptic device are smooth and stable, they must be updated at a rate greater than 500 Hz. Due to this time constraint, the majority of haptic docking tools do not attempt to model the conformational changes that would occur when molecules interact during binding. Our haptic-assisted docking tool, "Haptimol FlexiDock", models a receptor's conformational response to forces of interaction with a ligand whilst maintaining the required haptic refresh rate. In order to model receptor flexibility we use the method of linear response for which we determine the variance-covariance matrix of atomic fluctuations from the trajectory of an explicit-solvent Molecular Dynamics simulation of the ligand-free receptor molecule. Key to satisfying the time constraint is an eigenvector decomposition of the variance-covariance matrix which enables a good approximation to the conformational response of the receptor to be calculated rapidly. This exploits a feature of protein dynamics whereby most fluctuation occurs within a relatively small subspace. The method is demonstrated on Glutamine Binding Protein in interaction with glutamine, and Maltose Binding Protein in interaction with maltose. For both proteins the movement that occurs when the ligand is docked near to its binding site matches the experimentally determined movement well. It is thought that this tool will be particularly useful for structure-based drug design.

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“…Molecular docking simulation [27] can make the observer feel the interaction force in the docking process, thereby increasing the understanding of it. HaptiMol ISAS software to explore water accessible biomolecular surfaces [28,29], HaptiMol ENM to simulate haptic feedback by applying forces to individual atoms [30], and HaptiMol RD to simulate haptic feedback in molecular docking [31][32][33][34] are haptic softwares created with the CHAI3D haptic framework that supports a grounded haptic devices with translational force feedback. More sophisticated devices with rotational force feedback also exist [35,36].…”

Section: Virtual Reality Simulationmentioning

confidence: 99%

Tensegrity representation of microtubule objects using unified particle objects and springs

Pramudwiatmoko

Gutmann

Ueno

et al. 2020

CBIJ

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There are limitations in interactions with molecular objects in laboratory experiments due to the very small size of the objects. Common media to show the experimental results of molecular objects is still lack of observer interaction to understand it intuitively. In order to overcome this lack of interaction, this research takes tensegrity representation of molecular objects reproducing experimental results and creates interactive 3D objects to be presented in a virtual reality (VR) environment. The tensegrity representation enables us to enhance the interaction experience with the natural user interface with haptic technology and hand tracking controller. A particle simulation system that utilizes multiple GPUs resources is used to fulfill haptic VR requirements. We developed a unified particle object model using springs and particles which we call anchors which act as tensegrity structure of the object to support conformation of filament-type objects such as microtubules. Some object parameters can be set to match the flexural rigidity of the object with some experimental results. The bending shape of the object is evaluated using the classic bending equation and the results show high compatibility. Viscoelastic behavior also shows similarities with the viscosity reported in other studies. The object's flexural rigidity can be adjusted to match the target value with the direction of the prediction equation. The object model provides a better insight about molecular objects with natural and real-time interactions to provide a more intuitive understanding with the molecular objects presented. The results show that this model can also be applied to any filament-type or rod-like molecular object.

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Determination of locked interfaces in biomolecular complexes using Haptimol_RD

Cited by 5 publications

References 33 publications

Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics

Virtual Environment for Studying the Docking Interactions of Rigid Biomolecules with Haptics

Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility

Tensegrity representation of microtubule objects using unified particle objects and springs

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