Advances in Human-Protein Interaction - Interactive and Immersive Molecular Simulations [chapter]

Alex Tek, Matthieu Chavent, Marc Baaden, Olivier Delalande, Patrick Bourdot, Nicolas Ferey
2012 Protein-Protein Interactions - Computational and Experimental Tools  
2 www.intechopen.com 2 Will-be-set-by- IN-TECH an experimental result in MD. These constraints have to be defined a priori, rendering it difficult to explore all possibilities in order to examine various biological hypotheses. A new approach allowing to address these problems has emerged recently: Interactive Molecular Simulation (IMS). IMS consists in visualising and interacting with a simulation in progress, and provides the user with control over simulation settings in interactive time. With
more » ... the recent advances in human computer interaction and the impressive increase of available computing power, the IMS approach allows a user to interact in 3D space in real time with a molecular simulation in progress. This approach provides quality control features by visualizing results of a simulation in progress and supplies interactive features, such as feeling forces involved in the simulation as well as triggering specific events by applying custom forces during the simulation in progress. These advances led to a new generation of scientific tools to better understand life science phenomena, which place the human expertise at the centre of the analysis process, complementarily to automatic computational methods. The IMS approach emerged from the breakthrough initiated by the Sculpt precursor program proposed by Surles et al. (1994) . Since then, the interactive molecular simulations field has been developing continuously. Initial interactive experiments using molecular mechanics techniques gave quickly rise to "guided" dynamics simulations [ Wu & Wang (2002) ] or Steered Molecular Dynamics (SMD) [Isralewitz et al. (2001) ] [Leech et al. (1996) ]. The interest for these methods increased with the enhancement of simulation accuracy and thanks to the exciting new possibilities for dynamic structural exploration of very large and complex biological systems. In the Interactive Molecular Dynamics (IMD) approach, steering forces are applied interactively with a chosen amplitude, direction and application point. This enables the user to explore the simulation system while receiving instant feedback information from real-time visualisation or haptic devices [Leech et al. (1997) ]. Schulten's group has carried out several applications of IMS simulations to macromolecular structures [Grayson et al. (n.d.)] [Stone et al. (2001)]. This effort lead to the design of two efficient software tools facilitating the process of setting up an IMS : NAMD and VMD [Phillips et al. (2005)] [Nelson et al. (1995))]. The underlying exchange protocol is also supported by ProtoMol [Matthey et al. (2004)], LAMMPS [Plimpton (1995)], HOOMD-blue [Anderson et al. (2008)] and any software using the MDDriver library [Delalande et al. (2009)]. Similar projects proposing an interactive display for molecular simulations exist, such as the Java3D interface proposed in Knoll & Mirzaei (2003) and Vormoor (2001), or the Protein Interactive Theater [Prins et al. (1999)]. With fast generalization of new computer hardware devices and increasing accessibility to powerful computational infrastructures, IMS showes a fast and promising evolution, even for very large molecular systems (over 100.000 atoms). Such applications are now in the reach of state-of-art desktop computing. This evolution was possible given the strong increase in raw computing power leading to faster and bigger processing units (multi-processors, multi-core architectures). Currently ongoing technological developments such as GPU computing and the spread of parallelized entertainment devices (PS3, Cell) with specific graphic and processing capabilities open exciting new opportunities for interactive calculations. These approaches could provide even more processing power for highly parallelizable computational problems, for instance by differentiating the parallelisation of molecular calculations and graphical display functionalities. Given these developments, the range of accessible computational methods and representations is bound to grow. It may soon be possible to extend the IMS approach to ab initio or QM/MM calculations. Indeed, the precision achieved in the description of a system can be improved by switching to a more 28 Protein-Protein Interactions -Computational and Experimental Tools www.intechopen.com Advances in Human-Protein Interaction -Interactive and Immersive Molecular Simulations 3 accurate physical model and/or by improving the representation of the molecular context simulated. Thus, multi-scale simulations [Baaden & Lavery (2007) ] would indeed benefit from an interactive approach leading to important advantages with respect to the study of complex biological systems. However, the raw increase in computer speed alone is not sufficient to grant a successful future evolution of the IMS approach. In addition, it is necessary to develop adapted software solutions, which are generally more efficient [Grayson et al. (n.d.)], as it is commonly admitted in the numeric simulation field. Finally, the most recent and famous work illustrating the revolution of this approach is the "Fold It" serious game, which allows a user to interactively propose a protein folding solution [Cooper et al. (2010) ]. We will describe in this chapter the recent advances relating to these IMS approaches previously described. As IMS implies to efficiently combine simulation and interaction features, we will explain how we designed specific simulation, visualisation, and interaction techniques to solve the real time constraint, to study complex biomolecular systems, and to address a larger simulation timescale. Then we will discuss software architectures to efficiently put the different building blocks together. Finally, we will explain how we apply IMS to different fields of research including various topics such as protein-protein docking in a virtual reality and multimodal context, an ion substitution study using an haptic device, and a study about the opening and closure of the Guanylate Kinase enzyme. A rigid body simulation model to interactively study protein-protein interactions At a larger scale, it is sometimes not necessary to model and simulate the flexibility of a protein, but sufficient to consider the protein as a rigid body. Using a simple but accurate model at the macroscopic scale allows us to overcome the main constraint to provide an interactive time biophysical simulation as required for IMS: taking into account the user interaction during a simulation in progress. To present our rigid body simulation model dedicated to IMS, especially interactive rigid docking, we have to focus on the main phenomena that are involved in the protein interactions.
doi:10.5772/36568 fatcat:piy3kpfmmjf2xfmupn3umwg3am