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Studying the dissociation of Amyloid Forming Region in Yeast adhesin

posted Apr 8, 2015, 8:58 AM by Rajat Kumar Pal   [ updated Apr 9, 2015, 2:34 PM by Emilio Gallicchio ]

by Rajat Kumar Pal, Biochemistry Ph.D. candidate

Microbial adhesion is a crucial phenomena for the survival of microorganisms and competing with other microbial species in an ecological niche. At the same time, it is also a significant problem in the healthcare industry and much research has been done to understand the processes involved for development of therapeutic strategies. For a commensal yeast, Candida albicans, the nosocomial infections attributes to the adhesion of these organisms onto surgical instruments with the formation of biofilms with an approximate 40% mortality rate in immuno-compromised patients. Previous studies reported that the adhesion property in Candida sp. is partly due to the presence of cell-surface glycoproteins called Adhesins encoded by ALS gene family. Eight adhesins have been identified , Als1- Als7 and Als-9. All these Als proteins have a heptapeptide region with potential to form amyloid peptide designated as AFR. Cell-cell adhesion studies have demonstrated the involvement of this region in cell adhesion. In our study, we examined the free energy of dissociation of the AFR from the body of the adhesin Als3 which is believed to be the first step in amyloid formation. For this, we employed Metadynamics to simulate the dissociation of the AFR and calculated the free energy from the potential of mean force(PMF). The relative probabilities were calculated from trajectory analysis to measure the likelihood of the formation of AFR during the simulation. Understanding the free energy requirement for amyloid formation is a critical step towards studying the adhesion and pathogenesis of Candida albicans. A detailed report of the findings are provided in this report.

Abbreviation: ALS- Agglutinin like sequence; AFR – Amyloid forming region; PMF – potential of mean force

Rajat Kumar Pal,
Apr 8, 2015, 8:58 AM