Date of Award

2026-05-01

Degree Name

Master of Science

Department

Computational Science

Advisor(s)

Lela Vukovic

Abstract

This thesis investigates the structural and thermodynamic interactions between Perfluorodecanoic acid (PFDA) and bovine alpha-lactalbumin (ALAC), a critical milk protein essential for infant nutrition. The primary objectives were to computationally determine the most probable binding sites of PFDA to ALAC and to quantify the strength of these interactions alongside the structural changes they induce. This study addresses a critical gap in understanding how persistent environmental contaminants like PFDA are recruited and transported by nutritional proteins within the milk matrix. The methodology integrated high-throughput molecular docking with long-range, molecular dynamics (MD) simulations to provide a dynamic characterization of the ALAC-PFDA complex. Through systematic scanning and cluster analysis, two dominant binding sites were identified. MM/GBSA free binding energy calculations determined the PFDA binding energies to ALAC in those two binding sites. Simulations also reveal PFDA-induced conformational changes in Site 2 over time, where random coil of ALAC N-terminus wraps around the PFDA ligand. These results confirm that ALAC acts as an active vehicle for PFDA recruitment and emphasize that microsecond-scale sampling is essential to capture the cooperative maturation of the binding interface. Ultimately, these insights provide a definitive molecular basis for future research into the transport of perfluorinated contaminants and their impact on protein functional stability.

Language

en

Provenance

Received from ProQuest

File Size

48 p.

File Format

application/pdf

Rights Holder

Randhal Smith Ramirez Orozco

Download

Share

COinS