by Rajat Kumar Pal, Biochemistry Ph.D. candidateMicrobial 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 |
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