- Giuseppe Brancato (Scuola Normale Superiore, Pisa, Italy)
- Massimiliano Di Ventra (University of California, San Diego, USA)
- Marija Drndic (University of Pennsylvania, Philadelphia, USA)
- Maria Fyta (Institute for Computational Physics, University of Stuttgart, Germany)
- Tomoji Kawai (Osaka University, Japan)
- Branislav Nikolic (University of Delaware, Newark, USA)
Fondazione Monte dei Paschi di Siena
Introduction and motivation
Fast and low-cost DNA sequencing methods  have been on the scientific horizon sincethe first sequencing of the full human genome [2,3]. The past few years, in particular, have seen a surge of activities worldwide to make genome-based medicine ever closer toreality. Success in this field would represent a true revolution: a person could havehis/her full genome sequenced so that drugs could be tailored to his/her specific illnesses; doctors could know in advance patients’ likelihood to develop a given ailment; cures tomajor diseases could be found faster. However, this goal of “personalized medicine” is hampered today by the high cost and slow speed of DNA sequencing methods. Alternatives have been suggested that rely on physical and chemical approaches realized using nanoscale devices to probe DNA at the single-nucleotide level. This is in sharp contrast to current techniques and instruments that probe through chemical elongation, electrophoresis, and optical detection length differences and terminating bases of strands of DNA. Central to these novel approaches is the concept of nanochannels or nanopores, which allow for the confinement and control of DNA molecules.
For example, in the so-called third-generation DNA sequencing  via solid-state nanopores , single molecules of DNA are threaded through a nanopore or positioned in its vicinity and individual bases are detected as they pass through the nanopore. However, the development of solid-state nanopore-based DNA sequencing continues to struggle with a series of extremely challenging demands, in particular single-base resolution during the DNA translocation through the nanopore, optimized contrast in the electrical signals between the four different types of nucleotides, and a general improvement of signal-to-noise ratio [5-7].
Due to the high complexity of the problem at hand, theory and modeling  have been instrumental to explain experimental data, and most importantly to motivate and guide new experiments and novel biosensor designs [8,9]. In this context, the CECAM workshop will provide an ideal setting to gather international leaders with different background and expertise in order to exchange information and discuss together the future perspectives in this rapidly growing interdisciplinary research field.
State of the art
Right after the first sequencing of the human genome [2,3], an intense and growing research activity has been focused on the development of fast, inexpensive  and accurate methods for the DNA sequencing . Recently, both experimental and theoretical approaches, sometimes in close cooperation , have been exploited to make further steps towards such a fundamental goal for public health. In particular, several theoretical and computational methodologies, ranging from classical  and first-principles molecular dynamics [12,13] to multiscale methods [11,14,15] and first-principles simulations of electronic transport in nanopore- or nanochannel-based biosensors [7,9,16-19], could be fruitfully used to address some important phenomena related to DNA sequencing and detection at the molecular level.
For instance, a suggested approach to sequence DNA relies on the transverse transport properties of the different DNA bases while the DNA translocates through a nanochannel [6,16-23]. To simulate relevant effects in realistic biosensors of this type requires the calculation of quantum-mechanical tunneling currents coupled to molecular dynamics simulations of DNA translocation in electric fields [18,21]. Efficient theoretical approaches would be desirable that provide information on several phenomena related to the correlated motion of electrons and ions in real time.
Similarly, the effect of protonation of nucleobases while DNA translocates in confined geometries under the effect of strong electric fields is still a challenge to simulate fully from first principles . Moreover, other DNA detection techniques based on fast time-resolved spectroscopies can be possibly envisaged, e.g., by using powerful 2D optical spectroscopy [24,25]. In this regard, well sound theoretical models represent a fundamental prerequisite for the interpretation of complex spectroscopic data, as well as an invaluable tool for testing the feasibility of such approaches. Indeed, theoretical methods that are not yet available today could possibly play a very important role in the advance of future DNA-sequencing technologies. The increasing number of experiments  employing a wide variety of nanoprobes and materials hosting them [22,23,26] calls for such developments.
For example, single-particle Green function techniques coupled to density functional theory [27-31] have emerged as the workhorse computational algorithm to study electronic transport in complex systems. This methodology has been applied to a number of device concepts for DNA sequencing and detection [7-9,16-19]. However, present codes require substantial further development in order to become applicable to large (in excess of 10,000 atoms) systems [29,32] or setups [18,33] where electrostatic potential may be determined by a dynamical environment (such as a solvent). Even more demanding is computation of current and its noise in devices where many-body effects start to play an important role, as exemplified by electron-vibron interactions due to thermally fluctuating DNA and its environment [33,34].
In addition, there are several general open questions regarding the translocation of DNA in nanochannels [5,6,10] such as the effect of ionic currents in both detection and sequencing, the role of surface charges on the walls of the nanochannels, the ability to control the DNA translocation, hydrodynamic interactions in confined geometries, ... which await for theoretical enquiries.
The interest in the topics of DNA sequencing and detection is increasingly shared by physicists, chemists and biologists that traditionally have different backgrounds and belong to different communities with little communication. Besides pursuing biosensor development, this research also provides insight into fundamental physical processes that occur at the interface between solids, liquids and biomolecules. The CECAM workshop aims at bringing together an international group of leaders in the field of modeling the interaction between solids, liquids and bio-polymers and quantum transport in nanoelectronic biosensors.
The workshop participants will also benefit from the presence of several world-renowned experimentalists that will provide a broad overview of the experimental challenges and motivate discussions among theorists. This should foster a synergistic iterative process for the future where computation guides experiments and theory, while experiments and theory advance computation.
This workshop will be ideal to outline several key questions and set out a plan of attack for the coming years that would involve the whole scientific community. To this end, the interdisciplinary nature of this workshop will be a key ingredient in the solution of the high complexity problems we still face. Therefore, a closer interaction, as well as information exchange, among different research fields, such as biology, chemistry and physics, will be highly encouraged and a special effort in this direction will be required from all lecturers.
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