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Structural Biology 2018
Volume: 4
Biochemistry & Molecular Biology Journal
Page 45
March 15-16 2018
Barcelona, Spain
10
th
Edition of International Conference on
Structural Biology
P
roteins often perform a diverse and complex set of
functions within the cell, including catalyzing metabolic
reactions, transport of specific substances from one location
to another, etc. Therefore, proteins, also called biologics, are
regularly used in protein-based therapies to treat diseases.
A major potentiality of biologics resides in their intrinsic
compatibility with living systems, in comparison with
small molecule drugs. Biologics are often characterized
by high specificity and potency with low toxicity and thus
have interested many pharmaceutical industries. Several
challenges confront pharmaceutical scientists involved in the
development of protein therapeutics. For instance, the proper
stabilization of biologics is one of the major concerns. To
overcome this issue, excipients play a major role in stabilizing
biologics to prevent protein-protein interactions and hence
aggregation. Currently, a detailed molecular understanding
of the effect of different physicochemical formulation
conditions on the stability of proteins is sparse, as molecular
interactions are difficult to investigate experimentally at the
molecular level. Thus, computational approaches, as applied
in the current study, can provide insight on the single-molecule
level. This rational approach is an attempt to understand the
combined effect of pH and salinity on the protein stability. We
investigated the effect of pH and ionic strength on the wild-
type plectasin, and the three variants (PPI41, PPI42, PPI43).
Furthermore, independent protein thermodynamic integration
MD simulations were performed to understand conformational
stability due to the presence of cysteines bonds. These results
are further supported by NMR and fluorescence studies.
Additionally, studies have been performed to identify potential
hotspots for excipient-protein interactions using free energy
approaches such as implicit solvent molecular mechanics
(MM-PBSA) and explicit solvent linear interaction energy (LIE)
methods, relative binding affinities of excipients to the proteins
are predicted in order to rank excipients and to determine the
effect of excipients on protein dynamics and flexibility. These
results will be further supported by NMR studies.
Biography
Sowmya Indrakumar holds a Bachelor of Science (by Research) and Mas-
ter of Science degree in Biology from Indian Institute of Science, Bangalore,
India. Throughout her undergraduate studies, she was a recipient of ‘Inno-
vation in Science Pursuit for Inspired Research-Department of Science &
Technology (INSPIRE-DST) fellowship. In 2016, she became part of the PIP-
PI
(http://www.pippi.kemi.dtu.dk/)project as a Ph.D. researcher at Technical
University of Denmark, Denmark. This project has received funding from the
European Union’s Horizon 2020 research and innovation programme under
the Marie Skłodowska-Curie grant.
soemya@kemi.dtu.dkCharacterization of protein-excipient interactions for
designing formulation
Sowmya Indrakumar
1
, Pernille Harris
1
, Günther H J Peters
1
, Allan Nørgaard
2
and
Werner Streicher
2
1
Technical University of Denmark, Denmark
2
Novozymes A/S Denmark
Sowmya Indrakumar et al., Biochem Mol biol J, Volume 4
DOI: 10.21767/2471-8084-C1-009