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PLAGIARISM SCAN REPORT

Date 2021‐05‐21

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The molecular self‐assembly process is a reversible and spontaneous organization of molecular assemblies under
equilibrium conditions into stable conformations without any external forces involved. [1‐3]. These processes occur in
normal physiological as well as disease states. Examples include the formation of quaternary structure of haemoglobin and
trans‐membrane ion channels, to amyloids associated with Alzheimer’s disease [4‐8].
In this area, the weak intermolecular forces of attraction and conformational change are the main players in the initiation of
the biochemical cascade of metabolic reactions [9,10]. The understanding of the supramolecular interaction between host‐
guest interactions is a strategic is vital in drug design [11]. There are various other interactions to be taken into account at
the supramolecular level, such as hydrogen bonding, van der Waals interactions and hydrophobic interactions [12‐14].
Focusing on hydrophobic interactions, these are most stressed on and studied about in the design of new drugs as they
are key interactions between the host and guest. Even the inclusion of a simple methyl group can have deep implications
[15–18]. It was previously reported that such an inclusion resulted in higher affinity of oligonucleotide binding to RNA.
Brian Froehler also proved that such bindings could be improved be increasing the space available for stacking interactions
[19,20].
Some computational techniques in rational drug design enable the process of drug design to be less tedious, less time‐
consuming and more cost‐effective. Protein mobility, although it creates a hindrance to rational approaches to drug
design, and yet, by understanding the dynamics of the underlying process one can resolve the issue [21,22]. This is done by
analysis of protein crystal structures. In structure‐based drug design, focus is on the three‐dimensional structure, but
atomic displacement factors, known as the B‐, Debye‐Waller or temperature factors, are highly useful and they give atomic
resolution information on the structure mobility process [23]. However, the distribution of raw B‐factors is irregular
comparing different crystallographic sets and they need to be normalized [24] The normalized B‐factor ﴾B’‐factor﴿ is a
statistic expression of the raw experimental B‐factor for which different calculation methods have been developed [25‐27].
The BANΔIT toolkit ﴾https://bandit.uni‐mainz.de﴿was designed and developed for such a purpose. In case one wishes to
make use of the tool offline, the source code can be downloaded from https://github.com/FBarthels/BANDIT.
Even in the situation of the current COVID‐19 pandemic, computational tools have come to the rescue. SARS‐CoV‐2 is a
virus comprised of a single strand of RNA. [28,29]. The structural ﴾spike﴿ glycoprotein ﴾S﴿ on the viral coating is a promising
drug target as it is involved in attachment to the human cell and as well as entry into cells.
In the study by Shehroz et al., the active residues involved previously reported were used to design the pharmacophore
[30]. Upon virtual screening of the pharmacophore, 8 lead compounds were obtained that can disrupt interaction of RBM
of S with ACE2 and can prevent the entry of the virus into cells by disabling them from attaching to the host cell in the first
place. These findings need to be investigate clinically to check the actual efficacy.
However, though advances in computation are making breakthroughs in many areas, computational tools are currently
limited by the threat of drug resistance in humans.
In the study by Pritchard et al., they parameterized models of drug resistance and by studying the multiple variables
involved, showed that predictive evolutionary modelling can forecast population patterns of drug resistance without
requiring clinical trials. It was postulated that next‐generation drug design should evolve as follows: when evolution
favours the likeliest resistance mutation, so should drug discovery [31].
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