An update on the use of molecular modeling in dendrimers design for biomedical applications: are we using its full potential?

ABSTRACT

Introduction

Dendrimers are well-defined hyperbranched polymers built from a variety of different monomers and with tuneable properties that make them suitable for different biomedical applications. Their three-dimensional (3D) structure cannot be usually determined experimentally due to their inherent nature of repeating patterns in the topology, failure to crystalize, and/or high flexibility. Therefore, their conformations and interactions at the atomistic level can be studied only by using computational chemistry methods, including molecular dynamics, Monte Carlo simulations, and molecular docking.

Areas covered

In this review, the methods that could be utilized in computer-aided dendrimer design are considered, providing a list of approaches to generate initial 3D coordinates and selected examples of applications of relevant molecular modeling methods.

Expert opinion

Computational chemistry provides an invaluable set of tools to study dendrimers and their interactions with drugs and biological targets. There is a gap in the software development that is dedicated to study of these highly variable and complex systems that could be overcome by the integration of already established approaches for topology generation and open source molecular modeling libraries. Furthermore, it would be highly beneficial to collate already built 3D models of various dendrimers with corresponding relevant experimental data.

KEYWORDS:

• Dendrimer
• hyperbranched polymer
• molecular dynamics
• Monte Carlo simulation
• molecular docking
• computer-aided formulation design

Article highlights

• Molecular modelling methods are essential for understanding structures of dendrimers and their interactions with components of pharmaceutical and biological matrices.

• The reliable generation of dendrimer topologies and 3D coordinates are crucial for obtaining realistic results of computational experiments.

• Molecular dynamics and Monte Carlo simulations can be used to study conformations of the dendrimers.

• Molecular docking evaluates intermolecular interactions of dendrimers with either drugs to be encapsulated or biomacromolecules as target molecules.

• Molecular docking relies on coordinates derived from molecular dynamics simulations, but also provides starting system for molecular dynamics simulation of drug delivery systems.

• Computational chemistry is underused in the design of novel dendrimers and/or novel formulations, that is possibly due to the lack of dedicated software to model dendrimers.

• Collation of already generated 3D models of dendrimers and relevant experimental data would enable use of deep learning machine approaches.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Dr. Nuno Martinho for generating the images used to create Figure 2.

Declaration of interest

M. Zloh is an employee of Nanopuzzle Medicines Design Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.