SMOG 2 and OpenSMOG: Extending the limits of structure-based models

Applying simulations with structure-based (Go-like) models has proven to be an effective strategy for investigating the factors that control biomolecular dynamics. The common element of these models is that some (or all) of the intra/inter-molecular interactions are explicitly defined to stabilize an experimentally-determined structure. To facilitate the development and application of this broad class of models, we previously released the SMOG 2 software package. This suite allows one to easily customize and distribute structure-based (i.e. SMOG) models for any type of polymer-ligand system. Since its original release, user feedback has driven the implementation of numerous enhancements. Here, we describe recent extensions to the software and demonstrate the capabilities of the most recent version, SMOG v2.4. Changes include new tools that aid user-defined customization of force fields, as well as an interface with the OpenMM simulation libraries (OpenSMOG v1.0). To illustrate the utility of these advances, we present several applications of SMOG2 and OpenSMOG, which include systems with millions of atoms, long polymers and explicit ions. We also highlight how one can incorporate non-structure-based (e.g. AMBER-based) energetics to define a hybrid class of models. The representative applications include large-scale rearrangements of the SARS-CoV-2 Spike protein, the HIV-1 capsid in the presence of explicit ions, and crystallographic lattices of ribosomes and proteins. In summary, SMOG 2 and OpenSMOG provide robust support for researchers who seek to apply structure-based models to large and/or intricate biomolecular systems.

Polymer ligand binding to surface-immobilized gold nanoparticles: A fluorescence-based study on the adsorption kinetics

We report on a simple, fluorescence-based method for the investigation of the binding kinetics of polystyrene ligands, dispersed in an organic solvent, to substrate supported gold nanoparticles. For this purpose,...

Design of abiotic polymer ligand-decorated lipid nanoparticles for effective neutralization of target toxins in the blood

We developed abiotic polymer ligand (PL)-decorated lipid nanoparticles (LNPs) to improve PL mobility, decrease aggregation after capturing the target, and increase the blood circulation time to achieve highly effective toxin neutralization in vivo.

COMPLEXATION OF APPLE PECTIN, MODIFIED TO PHARMACOPHORE, WITH THE CATIONS MANGANESE (II) IN AQUEOUS SOLUTIONS

Complex formation in systems containing manganese (II), natural pectin and/or pectin modified by organic pharmacophores (nicotine, salicylic, 5-aminosalicylic, anthranilic acids) was studied by spectral (UV-, IR-, NMR 13C spectroscopy), potentiometric and viscometric methods. Method isomolar series and the molar relationship defined by the molar composition and the range of stability of metal complexes: pectin + nicotinic acid > pectin + acid 5-aminosalicylic > pectin + anthranilic acid > pectin + salicylic acid > native pectin. It is shown that the stability constant of metal complexes is significantly influenced by the reaction temperature and the structure of the pharmacophore. The presence of an amino group in the structure of an aromatic molecule increases the stability of metal complexes by 1.5–2 orders of magnitude. The standard thermodynamic characteristics (∆Hº; ∆Gº; ∆Sº) are calculated, which indicate that the processes of complexation in all cases are enthalpy-entropy favorable (∆Hº<0, ∆Sº>0) and proceed spontaneously (∆Gº<0). The influence of the structure of the drug compound in the polymer ligand on a number of physical and chemical properties of metal complexes was revealed. The data of NMR 13C and IR-spectra allow us to conclude that not only carboxyl groups but also hydroxyl functions of polymer matrices participate in the coordination interaction of pectin and/or pharmacophore-containing pectin with manganese (II) cations.