Adaptive resolution simulations of biomolecular systems.

In this review article, we discuss and analyze some recently developed hybrid atomistic-mesoscopic solvent models for multiscale biomolecular simulations. We focus on the biomolecular applications of the adaptive resolution scheme (AdResS), which allows solvent molecules to change their resolution back and forth between atomistic and coarse-grained representations according to their positions in the system. First, we discuss coupling of atomistic and coarse-grained models of salt solution using a 1-to-1 molecular mapping-i.e., one coarse-grained bead represents one water molecule-for development of a multiscale salt solution model. In order to make use of coarse-grained molecular models that are compatible with the MARTINI force field, one has to resort to a supramolecular mapping, in particular to a 4-to-1 mapping, where four water molecules are represented with one coarse-grained bead. To this end, bundled atomistic water models are employed, i.e., the relative movement of water molecules that are mapped to the same coarse-grained bead is restricted by employing harmonic springs. Supramolecular coupling has recently also been extended to polarizable coarse-grained water models with explicit charges. Since these coarse-grained models consist of several interaction sites, orientational degrees of freedom of the atomistic and coarse-grained representations are coupled via a harmonic energy penalty term. The latter aligns the dipole moments of both representations. The reviewed multiscale solvent models are ready to be used in biomolecular simulations, as illustrated in a few examples.

STOCK: structure mapper and online coarse-graining kit for molecular simulations.

We present a web toolkit STructure mapper and Online Coarse-graining Kit for setting up coarse-grained molecular simulations. The kit consists of two tools: structure mapping and Boltzmann inversion tools. The aim of the first tool is to define a molecular mapping from high, for example, all-atom, to low, that is, coarse-grained, resolution. Using a graphical user interface it generates input files, which are compatible with standard coarse-graining packages, for example, Versatile Object-oriented Toolkit for Coarse-graining Applications and DL_CGMAP. Our second tool generates effective potentials for coarse-grained simulations preserving the structural properties, for example, radial distribution functions, of the underlying higher resolution model. The required distribution functions can be provided by any simulation package. Simulations are performed on a local machine and only the distributions are uploaded to the server. The applicability of the toolkit is validated by mapping atomistic pentane and polyalanine molecules to a coarse-grained representation. Effective potentials are derived for systems of TIP3P (transferable intermolecular potential 3 point) water molecules and salt solution. The presented coarse-graining web toolkit is available at http://stock.cmm.ki.si.

ENZO: a web tool for derivation and evaluation of kinetic models of enzyme catalyzed reactions.

We describe a web tool ENZO (Enzyme Kinetics), a graphical interface for building kinetic models of enzyme catalyzed reactions. ENZO automatically generates the corresponding differential equations from a stipulated enzyme reaction scheme. These differential equations are processed by a numerical solver and a regression algorithm which fits the coefficients of differential equations to experimentally observed time course curves. ENZO allows rapid evaluation of rival reaction schemes and can be used for routine tests in enzyme kinetics. It is freely available as a web tool, at http://enzo.cmm.ki.si.