Steered Molecular Dynamics Simulations on Human beta Defensin Crossing Model Bacterial Lipid Membranes

Submission information

Submission Number: 173

Submission ID: 3942

Submission UUID: 73f73831-3131-42b1-a998-b2f42ab40cc7

Submission URI: /form/project

Created: Mon, 08/21/2023 - 06:03

Completed: Mon, 08/21/2023 - 06:10

Changed: Wed, 09/04/2024 - 15:23

Remote IP address: 146.75.253.174

Submitted by: Gaurav Khanna

Language: English

Is draft: No

Webform: Project

Project Title Steered Molecular Dynamics Simulations on Human beta Defensin Crossing Model Bacterial Lipid Membranes

Program CAREERS

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Tags molecular-dynamics (288)

Status Complete

Project Leader

Project Leader Liqun Zhang

Email zhangl@uri.edu

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Project Personnel

Mentor(s) Liqun Zhang

Student-facilitator(s) Cole Pepin

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Project Information

Project Description Human beta defensins (hBDs) are an important family of natural antimicrobial peptides (AMPs). They belong to the human innate immune system and have broad-spectrum of antimicrobial activities against yeast, fungi, and both Gram-positive and Gram-negative bacteria. It is widely accepted that hBDs kill bacteria by directly binding, disrupting bacterial lipid membrane, then forming pores. But the exact functional mechanism in molecular details is still elusive. Human beta defensins type 1 to 3 (abbreviated as hBD-1, hBD-2, and hBD-3) are the typical members in hBD family and they have distinct membrane crossing capabilities.

In this project, steered molecular dynamics simulations will be applied to predict the translocation of those three hBDs through explicit model Gram-negative membranes. The result will supply insight designing novel AMP based antibiotics in the future.

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Project Institution University of Rhode Island

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Anchor Institution CR-University of Rhode Island

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Start as soon as possible. No

Project Urgency Already behind3Start date is flexible

Expected Project Duration (in months) 6

Launch Presentation

Cole_Pepin_research_launch_presentation.pdf (267.17 KB)

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Wrap Presentation

Cole_Pepin_research_wrap_presentation.pdf (3.86 MB)

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Project Milestones

Milestone Title: Milestones #1
Milestone Description: Get familiar with Unity Linux system, NAMD simulation, and antimicrobial peptides by reading online documents and 1 to 2 related journal papers; launch presentation.
Completion Date Goal: 2023-10-31
Milestone Title: Milestone #2
Milestone Description: Set up human beta defensin type 1 to 3 embedding in model Gram-negative bacterial lipid membranes using CHARMM-gui online program; then run NAMD simulations to equilibrate the systems built;
Completion Date Goal: 2023-11-30
Milestone Title: Milestone #3
Milestone Description: Run steered MD simulations to pull hBD-1/hBD-2/hBD-3 out of
model bacterial lipid membranes;
Completion Date Goal: 2023-12-31
Milestone Title: Milestone #4
Milestone Description: Analyze structure, dynamics and free energy profiles from Steered MD simulations; compare results from different defensin simulations, and interpret the results;
Completion Date Goal: 2024-02-28
Milestone Title: Milestone #5
Milestone Description: Write project report, do presentation based on research findings, wrap up the project.
Completion Date Goal: 2024-03-31

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Final Report

What is the impact on the development of the principal discipline(s) of the project? Working on Steered Molecular Dynamics aids in showing the importance of biophysics research when it comes to the medical field. Although the biochemistry aspect of knowing how the human beta-defensin’s work with the human body is extremely important, it is also important to gain an understanding of how the peptides may move through the human body as well as bacterial cell membranes. To efficiently use the peptides biochemical properties to its potential, the biophysical properties must be understood. Working with the online programs also provided insight on how efficient it can be to simulate an experiment rather than testing an experiment in a lab. Although using actual peptides shows how they act in reality, that can cost a lot of money and time to secure the samples and run tests. Online simulations allows for many tests to be ran, at a fraction of the price of a real experiment, while still providing accurate results.

What is the impact on other disciplines? Working with the online programs also provided insight on how efficient it can be to simulate an experiment rather than testing an experiment in a lab.

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Lessons Learned A lesson I learned throughout my project was that it is important to do outside research on your own to solve problems. Unlike classes, there is not a known solution to find, so it is important to do additional research to find needed information such as creating a code that simplifies the simulations.

Overall results Overall, the results from the project showed that the dimer forms of the hBD’s performed better than the monomer forms. Each human beta-defensin had advantages over others in certain experiments, however the dimers always performed better than the monomers.