Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using haptics

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

doi:10.1016/j.jmgm.2015.06.003

Cited by 11 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The application is written in Visual C++, and uses the OpenGL library for 3D graphics rendering. It can compute the nonbonded interaction forces, in real time, either on the CPU or the GPU, using the cut-off-based force calculation methods proposed by Iakovou et al [ 34 , 35 ]. Both methods compute the forces using the set of inter-atomic interactions within a given cut-off distance, and utilize efficient proximity querying algorithms (optimized for CPU and GPU execution) in order to identify this set.…”

Section: Methodsmentioning

confidence: 99%

Determination of locked interfaces in biomolecular complexes using Haptimol_RD

2016

Self Cite

View full text Add to dashboard Cite

Interactive haptics-assisted docking provides a virtual environment for the study of molecular complex formation. It enables the user to interact with the virtual molecules, experience the interaction forces via their sense of touch, and gain insights about the docking process itself. Here we use a recently developed haptics software tool, Haptimol_RD, for the rigid docking of protein subunits to form complexes. Dimers, both homo and hetero, are loaded into the software with their subunits separated in space for the purpose of assessing whether they can be brought back into the correct docking pose via rigid-body movements. Four dimers were classified into two types: two with an interwinding subunit interface and two with a non-interwinding subunit interface. It was found that the two with an interwinding interface could not be docked whereas the two with the non-interwinding interface could be. For the two that could be docked a “sucking” effect could be felt on the haptic device when the correct binding pose was approached which is associated with a minimum in the interaction energy. It is clear that for those that could not be docked, the conformation of one or both of the subunits must change upon docking. This leads to the steric-based concept of a locked or non-locked interface. Non-locked interfaces have shapes that allow the subunits to come together or come apart without the necessity of intra-subunit conformational change, whereas locked interfaces require a conformational change within one or both subunits for them to be able to come apart.

show abstract

Section: Methodsmentioning

confidence: 99%

Determination of locked interfaces in biomolecular complexes using Haptimol_RD

2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…Modern GPUs (Graphics Processing Units) are, however, suited to this problem as a large number of computations can be performed in parallel. Haptimol RD, a docking system presented by Iakovou et al 48 , made use of the GPU to model rigid docking of two large molecules. 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.…”

Section: Interactive Dockingmentioning

confidence: 99%

“…Haptimol RD, a docking system presented by Iakovou et al 48 , made use of the GPU to model rigid docking of two large molecules. 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: 99%

Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility

Matthews

Kitao

Laycock

et al. 2019

J. Chem. Inf. Model.

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Adaptive GPU-accelerated force calculation for interactive rigid molecular docking using haptics

Cited by 11 publications

References 39 publications

Determination of locked interfaces in biomolecular complexes using Haptimol_RD

Determination of locked interfaces in biomolecular complexes using Haptimol_RD

Tensegrity representation of microtubule objects using unified particle objects and springs

Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility

Contact Info

Product

Resources

About