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\begin{document}

\title{Molecular binding of different classes of organophosphates to methyl
parathion hydrolase from Ochrobactrum species}



\author[1]{Thanyada Rungrotmongkol}%
\author[1]{Nayana Bhat}%
\author[2]{Bodee Nutho}%
\author[1]{Chonnikan Hanpaibool}%
\author[1]{Sarinya Hadsadee}%
\author[1]{Alisa Vangnai}%
\affil[1]{Chulalongkorn University Faculty of Science}%
\affil[2]{Mahidol University Faculty of Science}%


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  \date{May 25, 2024}


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\begin{abstract}
Methyl parathion hydrolase (MPH) is an enzyme of the metallo-\selectlanguage{greek}β-\selectlanguage{english}lactamase
superfamily, which hydrolyses a wide range of organophosphates (OP).
Recently, MPH has attracted attention as a promising enzymatic
bioremediator. The crystal structure of MPH enzyme shows a dimeric form,
with each subunit containing a binuclear metal ion center. MPH also
demonstrates metal ion-dependent selectivity patterns. The origins of
these patterns remain unclear but are linked to open questions about the
more general role of metal ions in functional evolution and divergence
within enzyme superfamilies. We aimed to investigate and compare the
binding of different OP pesticides to MPH with cobalt(II) metal ions. In
this study, MPH was modelled from \emph{Ochrobactrum} sp. with two
different classes of OP pesticides bound, including phosphomonoester
(methyl paraoxon and dichlorvos) and \emph{S}-substituted
thiophsphotriester (profenofos). The docked structures for each
substrate optimized by DFT calculation was selected and subjected to
atomistic molecular dynamics simulations for 500 ns. It was found that
alpha metal ions did not coordinate with all the pesticides. Rather, the
pesticides coordinated with less buried beta metal ions. It was also
observed that the coordination of beta metal ions was perturbed to
accommodate the bulky pesticides. The binding free energy calculations
and structure-based pharmacophore model revealed that all the three
substrates could bind well at the active site. However, profenofos
exhibits the stronger binding affinity to MPH in comparison to other two
substrates. Therefore, the ability of the \emph{in silico} analysis
presented here could be informative for increasing enzyme stability and
activity.%
\end{abstract}%



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\verb`MS2_final.docx`  available at \url{https://authorea.com/users/593437/articles/628459-molecular-binding-of-different-classes-of-organophosphates-to-methyl-parathion-hydrolase-from-ochrobactrum-species}

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