Modelling the Structure of a Protein Domain (N-terminal of XPB) Linked with Protein Synthesis, DNA Damage Repair, Rare Diseases, Cancer Therapeutics, and Tuberculosis
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).
Code (0)
등록된 구현이 없습니다.
Tasks
NERSimilar Papers 제목 키워드 기반
Exploring the Regulatory Function of the N-terminal Domain of SARS-CoV-2 Spike Protein Through Molecular Dynamics Simulation
SARS-CoV-2 is what has caused the COVID-19 pandemic. Early viral infection is mediated by the SARS-CoV-2 homo-trimeric Spike (S) protein with its receptor binding domains (RBDs) in the receptor-accessible state. We perfo…
Modulation of N- to C-terminal interactions enhances protein stability
Although, several factors have been attributed to thermostability, the stabilization strategies used by proteins are still enigmatic. Studies on recombinant xylanase which has the ubiquitous (\b{eta}/{\alpha})8 TIM (Trio…
Interpreting BERT architecture predictions for peptide presentation by MHC class I proteins
The major histocompatibility complex (MHC) class-I pathway supports the detection of cancer and viruses by the immune system. It presents parts of proteins (peptides) from inside a cell on its membrane surface enabling v…
MHC presentation predictionBinding-and-folding recognition of an intrinsically disordered protein using online learning molecular dynamics
Intrinsically disordered proteins participate in many biological processes by folding upon binding with other proteins. However, coupled folding and binding processes are not well understood from an atomistic point of vi…
Approximate learning of parsimonious Bayesian context trees
Models for categorical sequences typically assume exchangeable or first-order dependent sequence elements. These are common assumptions, for example, in models of computer malware traces and protein sequences. Although s…
Clustering