Molecular dynamics simulation of coarse-grained poly(L-lysine) dendrimers

Abstract

Poly(L-lysine) (PLL) dendrimer are amino acid based macromolecules and can be used as drug delivery agents. Their branched structure allows them to be functionalized by various groups to encapsulate drug agents into their structure. In this work, at first, an attempt was made on all-atom simulation of PLL dendrimer of different generations. Based on all-atom results, a course-grained model of this dendrimer was designed and its parameters were determined, to be used for simulation of three generations of PLL dendrimer, at two pHs. Similar to the all-atom, the coarse-grained results indicated that by increasing the generation, the dendrimer becomes more spherical. At pH 7, the dendrimer had larger size, whereas at pH 12, due to back folding of branching chains, they had the tendency to penetrate into the inner layers. The calculated radial probability and radial distribution functions confirm that at pH 7, the PLL dendrimer has more cavities and as a result it can encapsulate more water molecules into its inner structure. By calculating the moment of inertia and the aspect ratio, the formation of spherical structure for PLL dendrimer was confirmed.

pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation

“…Also, coarse-grained MD approaches using the MARTINI force field 73 exist for PLL. 72 The existing PLL and PGA studies employ dominantly a single force field. An exception is a recent 1 ns long MD simulation of l and d enantiomers of neutral poly(lysine) and poly(glutamic acid) with 5 and 10 repeat units.…”

Molecular dynamics simulation study of doxorubicin adsorption on functionalized carbon nanotubes with folic acid and tryptophan

“…The water molecules were modeled by using the tip3p model 55 , and 3295 water molecules to the DOX-Trp-FA-CNT system, 3362 water molecules to the DOX-Trp-CNT system, 3458 water molecules to the DOX-FA-CNT system, and 3351 water molecules to the DOX-CNT system were added. During these MD simulations, the temperature was maintained at 300 K by employing a V-rescale thermostat 56 , and the pressure was held at 1 bar by applying the Parrinello–Rahman algorithm 57 , 58 . The Leap–Frog integration algorithm was utilized to solve the equation of motion under periodic boundary conditions in all directions.…”

Encapsulation of anticancer drug doxorubicin inside dendritic macromolecular cavities: First-principles benchmarks

“…Due to the complexity of these systems, predictions of encapsulation energies, final structures, and elucidation of the nature of intermolecular forces between the host and guest molecule require advanced all-atom or coarse-grained molecular dynamics approaches based on carefully tailored force fields. [10][11][12] One guest molecule that could be proficiently used in the context of drug delivery to enhance its biological activity and possibly minimize the side effects is the popular pharmaceutical doxorubicin (DXR). Doxorubicin, an anthracycline antibiotic, is a very effective anti-tumor agent with a broad spectrum of applications.…”