  In this work, we develop first near-complete 3D models for NTD-hXPB - the
N-terminal protein domain of the human transcription factor XPB. The results
are very significant as NTD-hXPB plays a critical role in the synthesis of
proteins (specifically transcription) and DNA damage repair (specifically
nucleotide excision repair). NTD-hXPB is directly implicated in rare diseases
XP-B, XP-CS, and TTD2, whose symptoms include neurodegenerative disorders,
premature aging, and decreased fertility. NTDhXPB is also linked to anti-cancer
therapies. As a bi-product we derived 3D models of NTD-mXPB - homologue of
NTD-hXPB in mycobacterium tuberculosis aka MTB (causative agent of most cases
of tuberculosis, which surpassed HIV as #1 infectious disease killer in 2014).
These could be potential target for TB therapeutics. Our ab-initio modelling
protocol takes advantage of recent powerful advances (prediction of contact
residues) in protein structure modeling. Our protocol also includes human in
the loop, inspired by the prevailing theory that computational abilities of
human minds can be powerfully harnessed in engineering/problem-solving. Using
the developed models in this paper, we are able to propose significant insights
into (a) the role of NTD-hXPB in the process of transcription and DNA damage
repair (specifically NER), (b) the critical interactions of NTD-hXPB with
another co-labourer protein p52, (c) diseases associated with NTD-hXPB, and (d)
alterations in functionalities between NTD-hXPB (in human) and NTD-mXPB (in TB
pathogen).
