Session: 16-01-01: Government Agency Student Poster Competition

Paper Number: 150751

150751 - Simulations of the Effect of Raloxifene Protein Deformation 

Our bones, primarily made from collagen protein and apatite minerals, protect our internal organs and produce blood cells. Unfortunately, aging and bone degenerate diseases can decrease the amount of bone mass and mineral density in our body leading to osteoporosis. Selective estrogen receptor modulator (SERM) molecules reduce the detrimental effects of aging on bone by binding to estrogen receptors on bone cells, promoting calcium uptake, and increasing bone density. There is still research needed to understand the pathways of how SERM biomolecules interact with the components of biological tissues.

This work addresses the specific question of how a protein, such as collagen, interacts with Raloxifene, a SERM compound, during mechanical stretching of the protein.

To create the computer model of the specific protein, a Protein Data Bank (PDB) file, which lists the coordinates and/or velocities of the atoms, is downloaded from the RCSB.org website. The collagen protein "1K6F" was chosen as a suitable collagen molecule from the website. This file is then uploaded to the Visual Molecular Dynamics (VMD) computer program to obtain a Protein Structure (PSF) file. A CHARMM22 protein parameter file, used to determine the force fields within the system, is taken from the MacKerell website. Finally, a configuration file is used to reference all the above files and specify the simulation's temperature, pressure, time step, and duration for the Nanoscale Molecular Dynamics (NAMD) software to run. The temperature was 294 K and the pressure was kept variable. The timestep was 2 fs/step and the simulation ran for 20000 steps. To stretch the protein, Steered Molecular Dynamics (SMD) was used with the constant velocity pulling method. A separate user-created SMD file specifies the fixed SMD atom and the moving dummy atom. The configuration file confirms the velocity, direction, and output frequency for the SMD data.

From the simulations, a resulting force vs stretch curve can be documented for proteins both with and without raloxifene. We can consider the presence of water in the system and the hydrated system's response to raloxifene. The protein's deformed and undeformed configurations will be shown and analyzed. This allows us to understand the effect of raloxifene on the protein deformation mechanism.

In conclusion, the study's outcomes will contribute to the mechanistic design of compounds that modify protein deformation and ultimately lead to simulation models of collagen and hydroxyapatite composites underlying bone. The full collagen computer model will also be freely shared upon request from the author.

This work is supported by the NSF AWARD #1952993, NSF 23-605: Graduate Research Fellowship Program (GRFP), AAUW's Selected Professions Fellowships, and Purdue University.

Presenting Author: Chizaram Ugboh Purdue University

Presenting Author Biography: Chizaram is a second-year graduate student at Purdue University, pursuing a master's in Mechanical Engineering. Her research spans both the computational and experimental realms of solid mechanics. She is well-versed in creating computer models of biomaterials, polymers, and metals. Her experimental research involves micromechanics, where she uses nanoindentation and uniaxial tension testing to confirm computational data results. She is also very passionate about STEM education and has volunteered her time to teach, mentor, and inspire young students to pursue careers in science, technology, engineering, and mathematics. Through her work, she hopes to break down gender stereotypes and encourage more diversity in these fields. In the future, she looks forward to either researching the failure mechanics of innovative materials to improve material performance, safety, and sustainability, or collaborating with leading experts to create standards for newly developed materials.

Authors:

Chizaram Ugboh Purdue University