bHLH Transcription Factors Inhibitors for Cancer Therapy: General Features for In Silico Drug Design
I.F. Tsigelny, V.L. Kouznetsova, S.C. Pingle and S. Kesari
Affiliation: UCSD San Diego Supercomputer Center, 9500 Gilman Drive, La Jolla, CA 92093-0505, USA.
Numerous basic-helix-loop-helix (bHLH) transcription factors (TF) have been found to play important roles in
tumor growth and progression. Elucidation of the common features of these TFs can pave the road to possible therapeutic
intervention. The existing studies of possible inhibition of these TFs are concentrated on the development of peptides or
small molecules that inhibit their dimerization or prevent their DNA binding. The bHLH TFs have striking similarity in
many functionally important regions, such as the helical regions of TFs that interact with each other during dimerization
and have complementary sets of residues on both sides of a dimer. These are hydrophobic residues along with anionic and
cationic residues with complementary charges. Such complementarity also exists in other contact regions of the bHLH
TFs. They also have a very specific set of positively charged residues on the surface, which would contact DNA. Such
specificity defines a common concept for an in silico design of bHLH TFs inhibitors for a number of existing and important
Keywords: bHLH, cancer, computational drug design, drug-DNA interactions, drug–protein interactions, inhibitors, in silico,
protein dimerization, transcription factor.
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