Date of Award

2021-05-01

Degree Name

Master of Science

Department

Computational Science

Advisor(s)

Lin Li

Abstract

Fast and accurate calculations of the electrostatic features for highly charged biomolecules such as DNA, RNA, highly charged proteins, are crucial but challenging tasks. Traditional implicit solvent methods calculate the electrostatic features fast, but they are not able to balance the high net charges in the biomolecules effectively. Explicit solvent methods add unbalanced ions to neutralize the highly charged biomolecules in molecular dynamic simulations, which require more expensive computing resources. Here we developed a novel method, the Hybridizing Ions Treatment (HIT) method, which hybridizes the implicit solvent method with the explicit method to realistically calculate the electrostatic potential for highly charged biomolecules. This HIT method utilizes the ionic distribution from an explicit method to predict the bound ions. Such bound ions are then added in the implicit solvent method to perform the electrostatic potential calculations. In this study, two training sets were developed to optimize the parameters for the HIT method. The performance on the testing set demonstrates that the HIT method significantly improves the electrostatic calculations. The results on two molecular motors, myosin, and kinesin, reveal some mechanisms for the two molecular motor proteins and explain some previous experimental findings well. This HIT program can be widely used to study highly charged biomolecules, including DNA, RNA, molecular motors, and other highly charged biomolecules. The HIT package is available at http://compbio.utep.edu/static/downloads/download_hit.zip.The SARS-CoV-2 that caused Covid-19 has spread since the end of 2019. Its major effects resulted in nearly half a million deaths around the whole world. Therefore, understanding virulence mechanisms is important to prevent future outbreaks and for COVID-19 drug development. The envelope protein is an important structural protein affecting virus assembly and budding. The E protein pentamer is a viroporin, serving as ions transferring channel in cells. In this work, we applied MD simulations, topological and electrostatic analyses to study the effects of palmitoylation on the E protein pentamer. The results indicate the cation transferring direction is more like lumen to the cytosol. The structure of palmitoylated E protein pentamer is more stable while the loss of palmitoylation caused the pore radius to reduce and even collapse. The electrostatic forces on the two sides of palmitoylated E protein pentamer are more beneficial to attract cations in the lumen and to release cations into the cytosol. The results indicate the importance of palmitoylation, which can help the drug design for the treatment of COVID-19.

Language

en

Provenance

Received from ProQuest

File Size

73 p.

File Format

application/pdf

Rights Holder

Shengjie Sun

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