PMID- 36928665
OWN - NLM
STAT- MEDLINE
DCOM- 20230405
LR  - 20230405
IS  - 0948-5023 (Electronic)
IS  - 0948-5023 (Linking)
VI  - 29
IP  - 4
DP  - 2023 Mar 16
TI  - Dynamics of TUBB protein with five majorly occurring natural variants: a risk of 
      cortical dysplasia.
PG  - 100
LID - 10.1007/s00894-023-05506-7 [doi]
AB  - Beta-tubulin (TUBB) protein is one of the components of the microtubule 
      cytoskeleton that plays a critical role in the central nervous system. Genetic 
      variants of TUBB cause cortical dysplasia, a developmental brain defect 
      implicated in axonal guidance and the neuron migration. In this study, we assess 
      pathogenic variants (Q15K, Y222F, M299V, V353I, and E401K) of TUBB protein and 
      compared with non-pathogenic variant G235S to determine their impact on protein 
      dynamic to cause cortical dysplasia. Among the analyzed variants, Q15K, Y222F, 
      M299V, and E401K were noticed to have deleterious effect. Then, variant 
      structures were modeled and their affinity with their known cofactor 
      Guanosine-5'-triphosphate (GTP) was assessed which showed diverse binding 
      energies ranged between (-7.436 to -6.950 kcal/mol) for the variants compared to 
      wild-type (-7.428 kcal/mol). Finally, the molecular dynamics simulation of each 
      variant was investigated which showed difference in trajectory between the 
      pathogenic and non-pathogenic variant. Our analysis suggests change in amino acid 
      residue of TUBB structure has notably affects the protein flexibility and their 
      interactions with known cofactor. Overall, our findings provide insight on the 
      relationship between TUBB variants and their structural dynamics that may cause 
      diverse effects leading to cortical dysplasia.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Janakiraman, V
AU  - Janakiraman V
AD  - Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, 
      Chettinad Hospital and Research Institute, Chettinad Academy of Research and 
      Education, Kelambakkam, 603103, Tamil Nadu, India.
FAU - Sudhan, M
AU  - Sudhan M
AD  - Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, 
      Chettinad Hospital and Research Institute, Chettinad Academy of Research and 
      Education, Kelambakkam, 603103, Tamil Nadu, India.
FAU - Alzahrani, Khalid J
AU  - Alzahrani KJ
AD  - Department of Clinical Laboratories Sciences, College of Applied Medical 
      Sciences, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
FAU - Alshammeri, Saleh
AU  - Alshammeri S
AD  - Department of Optometry, College of Applied Medical Sciences, Qassim University, 
      Buraydah, Saudi Arabia.
FAU - Ahmed, Shiek S S J
AU  - Ahmed SSSJ
AD  - Drug Discovery and Multi-Omics Laboratory, Faculty of Allied Health Sciences, 
      Chettinad Hospital and Research Institute, Chettinad Academy of Research and 
      Education, Kelambakkam, 603103, Tamil Nadu, India. shiekssjahmed@gmail.com.
FAU - Patil, Shankargouda
AU  - Patil S
AD  - College of Dental Medicine, Roseman University of Health Sciences, South Jordan, 
      UT, USA.
LA  - eng
PT  - Journal Article
DEP - 20230316
PL  - Germany
TA  - J Mol Model
JT  - Journal of molecular modeling
JID - 9806569
RN  - 0 (Tubulin)
SB  - IM
MH  - Humans
MH  - *Malformations of Cortical Development/genetics
MH  - Molecular Dynamics Simulation
MH  - *Tubulin/genetics/metabolism
MH  - Axon Guidance/genetics
OTO - NOTNLM
OT  - Cortical dysplasia
OT  - MD simulation
OT  - Molecular modeling
OT  - Natural variants
OT  - TUBB
EDAT- 2023/03/18 06:00
MHDA- 2023/03/22 06:00
CRDT- 2023/03/17 09:23
PHST- 2022/09/23 00:00 [received]
PHST- 2023/03/09 00:00 [accepted]
PHST- 2023/03/17 09:23 [entrez]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
AID - 10.1007/s00894-023-05506-7 [pii]
AID - 10.1007/s00894-023-05506-7 [doi]
PST - epublish
SO  - J Mol Model. 2023 Mar 16;29(4):100. doi: 10.1007/s00894-023-05506-7.