Molecular Modeling to Study Dendrimers for Biomedical Applications

Abstract

Molecular modeling techniques provide a powerful tool to study the properties of molecules and their interactions at the molecular level. The use of computational techniques to predict interaction patterns and molecular properties can inform the design of drug delivery systems and therapeutic agents. Dendrimers are hyperbranched macromolecular structures that comprise repetitive building blocks and have defined architecture and functionality. Their unique structural features can be exploited to design novel carriers for both therapeutic and diagnostic agents. Many studies have been performed to iteratively optimise the properties of dendrimers in solution as well as their interaction with drugs, nucleic acids, proteins and lipid membranes. Key features including dendrimer size and surface have been revealed that can be modified to increase their performance as drug carriers. Computational studies have supported experimental work by providing valuable insights about dendrimer structure and possible molecular interactions at the molecular level. The progress in computational simulation techniques and models provides a basis to improve our ability to better predict and understand the biological activities and interactions of dendrimers. This review will focus on the use of molecular modeling tools for the study and design of dendrimers, with particular emphasis on the

Perspective: Dendrimer drugs for infection and inflammation

“…The structural data generated from these molecular dynamics simulations also provides valuable biological insights. The subject has been discussed in detail in our papers [51e61] and in two recent reviews [62,63]. The power of this approach is considerable in providing important insights into parameters such as dendrimer size, shape, architecture, surface chemistry, and rigidity and flexibility.…”

Effect of PEGylation on the Structure and Drug Loading Capacity of PAMAM-G4 Dendrimers: A Molecular Modeling Approach on the Complexation of 5-Fluorouracil with Native and PEGylated PAMAM-G4

“…[9a],[10a], However, there is still a lack of information concerning the optimum PEGylation degree that maximizes the encapsulating properties of PAMAM dendrimers, and the molecular mechanistic aspects underlying the drug association with PEGylated PAMAM systems. In this scenario, molecular modeling approaches offer a valuable tool to enrich the molecular understanding about complexation phenomena and to provide structural, dynamic and thermodynamic information that can be translated into useful knowledge for the rational design and optimization of new drug carriers based on PEGylated PAMAM dendrimers …”

“…To date, molecular dynamics (MD) simulations have been extensively employed to deal with the structure and dynamic properties of PAMAM dendrimers of different generation . However, there is considerably lesser information concerning the use of MD simulations to deal with complexation phenomena in drug–PAMAM systems.…”

Rational design of novel, fluorescent, tagged glutamic acid dendrimers with different terminal groups and in silico analysis of their properties

“…The latter is particularly difficult to develop due to the diversity and high degree of chemical space that dendrimers encompass. Several degrees of complexity from coarse grained to full-atom simulations 21,22 have been utilized to understand how dendrimers interact with drugs and other biomolecules at the molecular interface. In this regard, molecular dynamics (MD) simulations have been shown to be a suitable method to predict the behavior of dendrimers and structure 15,22 and therefore are useful for the rational design of dendrimers.…”