Date of Award

May 2016

Degree Type


Embargo Date


Degree Name

Master of Science (MS)


Biomedical and Chemical Engineering


Shikha Nangia

Second Advisor

Arindam Chakraborty

Subject Categories



Molecular dynamics simulations have proven to be a breakthrough approach in providing molecular structure and function details of biological macromolecules. The fact that molecular simulations can provide details of individual particle motions as a function of time, opens infinite possibilities of answering specific questions about a model system with atomistic and molecular precision, often more easily than experiments on the actual system. Instead of relying solely on experiments, molecular dynamics systems are based on empirical force fields that mimic molecular interactions over time. There has been increasing interest in utilizing the multiscale molecular dynamics (MD) approach to simulate the properties of biological macromolecules for meaningful applications in areas of nanotoxicity, nanotherapy, and nanomedicine.

Recent advances in nanomedicine have led to the great development of several drug-delivery platforms for targeted delivery. Polymeric drug delivery systems are designed and applied to ameliorate undesirable properties of the drug agents such as hydrophobicity, poor targeting ability, and broad scale toxicity. However, rational structural design of polymeric nanocarrier is only based on theoretical investigation, that restraint by absence of real molecular-level details. So, MD approach is used to provide those desirable details which not feasible in experiments. In our work, models of three generations of anticancer nanocarriers polymer were developed and characterized using multiscale MD simulations. The results were compared to in vitro experimental results. Observations were analyzed and found to be in good agreement with experiments results on size and morphology changes. Details shown by our systems helped us discover the reasons for the different nanocarriers’ performances. Our results show the in silico methods that can be used to contribute to drug nanocarrier design optimization work.

Claudins, are critical components in building tight junctions (TJs) which could form paracellular channels or barriers for physiological functions. Recently, 27 types of claudins have been classified based on different functions and characteristics, and they are becoming potential points in developing drug delivery systems and pathological studies. However, the architecture of claudin strand in TJs is still unclear thus impeding further study and applications. So, we use MD simulation approach to replicate self-assembly process and try to find out the potential construction models. In our work, claudin-1, -2, -5, and -15 monomer models were built by homology modeling and validated. Self-assembly processes of non-mutated and mutated claudins were conducted to reproduce the construction of claudin macromolecular strands. Four classified dimer models predicted by existing research were found to be reproduced in our molecular dynamics systems, and their number distributions were calculated. Our results first time showed the potential models for TJ architectures that can be a guidance for understanding TJs.


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