Investigating the Stability of the LigAB Dimer Interface with Molecular Dynamics Simulations

Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

Kate Luo
Kate Luo

Kate Luo is a rising senior (’21) from Wellesley, MA. She first discovered her passion for chemistry as a student at Wellesley High School. Since graduating in 2017, she has continued to pursue her academic interests at Wesleyan with a double major in Chemistry and Neuroscience and Behavior. Outside of the classroom, she enjoys playing violin in the orchestra and various chamber ensembles. More interestingly, as she has been told in the past, she is a Zumba instructor and the coordinator of WesBAM. She is also the financial manager of the Asian American Student Collective and, consequently, a fiend on WesNest. Currently, she is anxiously awaiting replies from medical schools and hoping one will at least acknowledge her existence.

Abstract: Protein dimerization has been shown to play an integral role in many biological functions, from regulation of cellular mechanisms to forming important enzymatic structures. The enzyme LigAB is a homodimer of heterodimers of which the active site is located at the heterodimeric interface. In previous mutagenesis experiments, it was observed that certain mutations of the Phe103α residue, notably alanine and serine, prevented LigAB from co-purifying as a heterodimer. This finding indicated the potential to disrupt stability at the dimeric interface in the absence of a large, non-polar residue at this particular position. Because the dimeric interface is also the site of catalysis, altered stability of mutants could also affect their enzymatic activity. Using the GROMACS molecular dynamics package, the relative stability of the dimer interface was determined for various mutants. Fluctuation values were mapped and compared to corresponding values in wild type, looking specifically at residues known to occupy the active site and allosteric pockets. By comparing these values and additional binding free energy calculations to experimental data, more information about the stability of the dimer interface can be elucidated, specifically which residues or interactions might be crucial for co-purification of the dimer.

KLuo_Summer2020_Poster-Kate-Luo

Live Poster Session: Zoom Link
Thursday, July 30th 1:15-2:30pm EDT

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