Ions, membrane and channels: Multiscale simulations from quantum to coarse-grain. A symposium in honor of Mike Klein’s 80th birthday.
- Carmen Domene (University of Bath, United Kingdom)
- Paolo Carloni (Forschungszentrum Jülich, Germany)
- Halima Mouhib (Université Paris-Est Marne-La-Vallée, France)
- Giuseppe Brancato (Scuola Normale Superiore, Pisa, Italy)
Ion channels are proteins located in the cell membrane forming a passageway that extends along the otherwise impermeable lipid bilayer. They have the ability to open and close in response to chemical or physical stimuli, and they are selective to particular ions. Therefore, ion channels play a central role in the regulation of many physiological processes, and thus are major drug targets. With remarkable progress in the experimental determination of structures at atomic resolution together with the relentless development of computational algorithms, the increasing speed and availability of supercomputers and new hardware technologies, it is now possible to investigate a substantial number of biological phenomenon where ion channels are involved using computer simulation. To advance in this area, a critical review of the computational techniques traditionally employed is crucial and this is one of the goals of the meeting, as well as identifying perspective ones by borrowing ideas from other fields.
Five specific areas will be addressed:
 We will discuss the development of polarizable force fields and QMMM schemes as well as CG methodologies that have been use less often in this area.
 A powerful strategy to model systems on different scales (temporal and spatial) is to use a multiscale approach. How to link the different levels will be examined.
 How to optimize algorithms for accelerating state transitions in atomistic simulations of ion channels.
 The potential of mean force along a limited set of reaction coordinates is essential for understanding the evolution of complex system such as ion channels. Having appropriate reaction coordinates is paramount for efficient spatial and temporal sampling. How to estimate these energy maps accurately and efficiently and how to take advantage of this information to link models at different scales will be considered.
 Membrane currents have historically been modelled by Markov models estimated from experimental data. As much work has been done in the development and use of Markov state models to describe complex processes, we expect a lively discussion on whether and when one should try to identify a single reaction coordinate or try to construct Markov models using many metastable states.
The main objectives are:
• Deliver the newest technical approaches, and stimulate further developments as well as future collaborations in experimental and computational methods to simulate full spatial and temporal information. Current modelling software does not allow building and simulating multiscale models without having to become involved with underlying technical details.
• Identify challenges, priorities and opportunity areas in the multiscale modelling of ion channels. This is expected to trigger appropriate intellectual and joint grant opportunities, and lead to the establishment of novel research directions capable of maximizing the impact of the field in the near future.
The workshop is dedicated to Mike Klein in his 80th birthday, a leading scientist in many fields of science, including the molecular simulation of ions, membranes, and ion channels.