Haptic-driven, interactive drug design: implementing a GPU-based approach to evaluate the induced fit effect

Abstract

In this paper, we describe a hybrid meta-heuristics method of energy minimization and conformational sampling and its application into our haptic-driven molecular modelling simulator. The proposed method has been designed to suit real-time molecular docking simulations, where the time-lapse between two successive ligand poses is relatively small. In these situations, the energy minimization problem becomes increasingly complex and chaotic. The algorithm is tuned to take advantage of recent advances in GPU computing with asynchronous kernel execution, which has allowed us to include full protein flexibility in the real-time interactive, haptic-driven simulations. Finally, in this paper, we will also discuss the implementation of such high-performance computing approaches in our software, discussing the results of our initial validation studies, highlighting the advantages and limitations of such interactive methodology.

Wielding the power of interactive molecular simulations

“…88 The review paper on Haptic-driven Applications to Molecular Modeling provides an overview of haptic-driven molecular modeling software of the last decade that supports IMD and quantum mechanical calculations in addition to molecular docking applications 89,90 that the authors expanded later on. 91 In Table 1, we present a similar summary table. The tools were selected based on the arbitrary choice of a Field Citation Ratio higher than 1 of the reference papers.…”

The Matter Simulation (R)evolution

“…Emerging technologies that enhance the human–machine interaction will allow for an unprecedented immersion into the virtual atomistic world that is otherwise inaccessible to the human senses. Already today, we see haptic and tracking devices, virtual realities, and caves adding a new level of intuition to the virtual experience of the molecular world that goes far beyond its archaic and fractured perception through computer mouse and keyboard. − A perfect and seamless immersion of the scientist into the mesoscopic environment of her/his object of study is key to an accelerated understanding and manipulation of (molecular) matter in a virtual laboratory. For instance, immersion is about literally feeling the softness of a functional group in a molecule and about experiencing how it feels to push a hydrogen atom into a metal surface.…”

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

“…However, the system rendered van der Waals forces only and allowed the ligand to deform only when in contact with the rigid receptor. Recently, Anthopoulos et al 28 attempted to address protein−ligand flexibility to some degree, while evaluating the induced-fit effect during 3dof protein−drug docking. Even though they employed GPU-parallel-processing in order to accelerate the underlying computations, their approach could not satisfy the refresh rate requirements of the haptic device since it ran at only 33 Hz.…”