Knowledge of the spatial structure of a protein is essential for
determining its biological activity and critical for the design of drugs using
In Silico techniques. Despite the significant advances in protein structure
prediction based on a specific amino acid sequence achieved by the AlphaFold
technique based on artificial intelligence through the introduction of
artificial intelligence (deep learning) methods in 3D structure prediction
methodology, the question concerning the mechanism of the folding process
remains unanswered. In the current work, achieving an appropriate ordering of
the hydrophobicity distribution in the 3D structure was identified as a
determining factor for protein structuring. This paper discusses the
structuring process as dependent on two factors: external (environment like
water or membrane for example) and internal force field (non-bonding
interaction in protein body). The objects of the analysis are proteins with a
single mutation showing a different secondary structure and an example of the
chameleon sequence, where certain segments with an identical sequence adopt
different forms of secondary structure. The paper presents a theoretical model
with appreciation to Protein Data Bank and ChSeq databases. The analysis used
the fuzzy oil drop model in its modified version (FOD-M). The analysis was
performed with In Silico techniques using software of open access status. The
importance of the environmental contribution was demonstrated by four proteins
with targeted single mutations leading to a change in secondary structure from
helical to β. It has also been demonstrated in the example of chameleon
sequences with segments of 7 amino acids of identical sequence take adopt
different forms of secondary structure. The role of environmental conditions in
the folding process was demonstrated quantitatively with a mathematical
function, the optimization of which should lead to a structure with a defined
biological function. The application of the discussed model introduces the
possibility of controlling the folding process. The analysis supports the
hypothesis of the folding process as the effect of consensus between the
internal force field (non-bonding interaction in the protein body) and external
force field which directs the process toward the structure appropriate for
environment specificity (water/membrane).
Author
(s) Details
Roterman I
Department of Bioinformatics and Telemedicine, Jagiellonian University –
Medical College, 30-688 Krakow, Medyczna 7, Poland.
Dulak D
ABB Business Services Sp. z o.o., ul. Zeganska 1, 04-713 Warszawa, Poland.
Slupina M
ALSTOM ZWUS Sp. z o.o., Modelarska 12, 40-142, Katowice, Poland.
Stapor K
Department of Applied Informatics, Silesian University of Technology,
Gliwice, Poland.
Konieczny L
Chair of Medical Biochemistry, Jagiellonian University – Medical College,
31-034 Krakow, Kopernika 7, Poland.
Please see the book here:- https://doi.org/10.9734/bpi/cbrp/v3/4436
