An up-to-date overview of the CFOUR program system is given. After providing a brief outline of the evolution of the program since its inception in 1989, a comprehensive presentation is given of its well-known capabilities for high-level coupled-cluster theory and its application to molecular properties. Subsequent to this generally well-known background information, much of the remaining content focuses on lesser-known capabilities of CFOUR, most of which have become available to the public only recently or will become available in the near future. Each of these new features is illustrated by a representative example, with additional discussion targeted to educating users as to classes of applications that are now enabled by these capabilities. Finally, some speculation about future directions is given, and the mode of distribution and support for CFOUR are outlined.

We present Tinker-HP, a massively MPI parallel package dedicated to classical molecular dynamics (MD) and to multiscale simulations, using advanced polarizable force fields (PFF) encompassing distributed multipoles electrostatics. Tinker-HP is an evolution of the popular Tinker package code that conserves its simplicity of use and its reference double precision implementation for CPUs. Grounded on interdisciplinary efforts with applied mathematics, Tinker-HP allows for long polarizable MD simulations on large systems up to millions of atoms. We detail in the paper the newly developed extension of massively parallel 3D spatial decomposition to point dipole polarizable models as well as their coupling to efficient Krylov iterative and non-iterative polarization solvers. The design of the code allows the use of various computer systems ranging from laboratory workstations to modern petascale supercomputers with thousands of cores. Tinker-HP proposes therefore the first high-performance scalable CPU computing environment for the development of next generation point dipole PFFs and for production simulations. Strategies linking Tinker-HP to Quantum Mechanics (QM) in the framework of multiscale polarizable self-consistent QM/MD simulations are also provided. The possibilities, performances and scalability of the software are demonstrated via benchmarks calculations using the polarizable AMOEBA force field on systems ranging from large water boxes of increasing size and ionic liquids to (very) large biosystems encompassing several proteins as well as the complete satellite tobacco mosaic virus and ribosome structures. For small systems, Tinker-HP appears to be competitive with the Tinker-OpenMM GPU implementation of Tinker. As the system size grows, Tinker-HP remains operational thanks to its access to distributed memory and takes advantage of its new algorithmic enabling for stable long timescale polarizable simulations. Overall, a several thousand-fold acceleration over a single-core computation is observed for the largest systems. The extension of the present CPU implementation of Tinker-HP to other computational platforms is discussed.

We provide a perspective of the induced dipole formulation of polarizable QM/MM, showing how efficient implementations will enable their application to the modeling of dynamics, spectroscopy, and reactivity in complex biosystems.

Continuum solvation models are widely used to accurately estimate solvent effects on energy, structural and spectroscopic properties of complex molecular systems. The polarizable continuum model (PCM) is one of the most versatile among the continuum models because of the variety of properties that can be computed and the diversity of methods that can be used to describe the solute from molecular mechanics (MM) to sophisticated quantum mechanical (QM) post-self-consistent field methods or even hybrid QM/MM methods. In this contribution, we present a new formulation of PCM in terms of a free energy functional whose variational parameters include the continuum polarization (represented by the apparent surface charges), the solute’s atomic coordinates and—possibly—its electronic density. The problem of finding the optimized geometry of the (polarized) solute, with the corresponding self-consistent reaction field, is recast as the minimization of this free energy functional, simultaneously with respect to all its variables. The numerous potential applications of this variational formulation of PCM are discussed, including simultaneous optimization of solute’s geometry and polarization charges and extended Lagrangian dynamics. In particular, we describe in details the simultaneous optimization procedure and we include several numerical examples.