GADDLE Maps: General Algorithm for Discrete Object Deformations Based on Local Exchange Maps

Abstract

A new method for switching between structures consisting of equivalent discrete and flexible objects with different particle representation and object configuration, including different resolution levels (number of particles per object), is reported. The method is fully general since it does not require any extra code nor additional database elements for new systems. It is based on a Monte Carlo sampling of the configurational space for each object type of the target system. The sampling is controlled by a Metropolis acceptance criterion of movements (translations, rotations, and relative deformations of the object configuration) that uses the generalized distance between the sets of particles at both representations. For Gaussian distributed distances, such a minimization procedure is equivalent to an optimization of χ in a maximum likelihood method. This provides sound statistical support since the method leads to the most probable configuration of the system at each representation. The configurations obtained in this way are then used to create resolution exchange maps for each object type, which allows the extrapolation of the conversion to every object configuration throughout the whole system. As an example, the method is here tested with several molecular dynamics simulated systems (ionic liquids, cyclodextrins, cell-penetrating peptides, cyclic peptides, lipid bilayers, vesicles, heterogeneous organic molecules, DNA, and solvated proteins) for different resolution force fields (GROMOS, AMBER, OPLS, MARTINI) using GROMACS. In this context, the method can be applied to map structures described by any other pair of force fields, as well as to homogeneous and heterogeneous systems with many different molecules. The method is proved to be highly efficient since the time required for the mapping is practically independent of the number of molecules in the target system.

In Vitro–In Silico Modeling Approach to Rationally Designed Simple and Versatile Drug Delivery Systems

“…For sphingomyelin (SM), we took the parameters for C­(18:1/18:0), ,, deleting one of the beads to make it more similar to the one used experimentally [C­(18:0/16:0)]. The CG systems were mapped back to AT resolution using GADDLE Maps, a novel algorithm implemented recently in our group . After re-solvation with pre-equilibrated water, AT simulations were carried out using GROMOS54a7_atb …”

“…The loss of resolution associated with CG simulations can be overcome by performing multiscale simulations taking advantage of the best features of each simulation level. In this regard, we have recently developed a new method, the GADDLE Maps algorithm, to switch between different representations of systems consisting of discrete and flexible objects, that has been validated by recovering AT representations of a number of molecular systems, starting from CG-level representations . In view of this information, we propose here the development of a novel type of nanosystem, VSNs, based on only two naturally occurring materials: vitamin E (V), an antioxidant and a widely used generally recognized as a safe (GRAS)-listed excipient with a well-known safety record, and sphingomyelin (SM), a major component of cell membranes that has already been used in the preparation and commercialization of the nanomedicine Marqibo, formulated by a very mild low-energy methodology.…”

“…The CG systems were mapped back to AT resolution using GADDLE Maps, a novel algorithm implemented recently in our group. 14 After re-solvation with pre-equilibrated water, AT simulations were carried out using GROMOS54a7_atb. 35 2.2.2.…”

Initiating Coarse-Grained MD Simulations for Membrane-Bound Proteins

“…There is a program called cg2at, written by Phillip Stansfeld [34]; however, this software is not open source. Three open-source tools are the program backward.py [35] (https://github.com/Tsjerk/ Backward), or the website CHARMM-GUI [36] the website Gaddlemaps [37] (http://fmtriton2.usc.es/). All have their advantages and disadvantages.…”

Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes

“…Using this approach, it is more difficult to describe the behavior of other molecules -such as proteins or DNA-in a realistic way, so internal restraints are typically used to overcome obvious artifacts [14]. In any case, the atomistic structure of the systems simulated at CG resolution can be recovered by applying different algorithms [15,16]. CG parameterizations of CDs have been made in the past [17] but they are not expected to be fully reliable since the larger van der Waals radius of CG beads significantly reduces the volume of the cavity, thus seriously affecting their ability to encapsulate molecules as well as the accessible conformational space of the system.…”