Background: Estrogen receptor-α (ERα) positive breast cancer is considered to be one of the most
common metastatic diseases. Estrogenic signalling in breast cancer is one of the most critical oncogenic
pathways. Recently Lemur Tyrosine Kinase 3 (LMTK3) was identified as a potential oncogenic ERα
regulator with a significant role in endocrine resistance. Therefore, targeting LMTK3 in breast cancer
would control ERα modulation and may provide a better diagnostic development and a new therapeutic
target to fight these resistant and aggressive tumours.
Objective: The study aimed to understand the salient structural features of LMTK3 using molecular dynamics
Methods: In this computational study, we modelled 3D structure of LMTK3 domain using Iterative
Threading ASSembly Refinement (I-TASSER) and studied conformational dynamics using molecular
dynamics simulation. We used online computational tools and software to perform comprehensive investigation
on the cavities, hydrophobicity, electrostatic potential, secondary structure topology and intra-
molecular interactions in LMTK3.
Results: The LMTK3 structure was observed to be stable during Molecular Dynamics (MD) simulation.
We also predicted the probable binding cavities in LMTK3. In addition, we determined hydrophobic
clusters and patches in LMTK3 which may be crucial for folding and stabilisation. Possible interaction
sites in LMTK3 were then studied by electrostatic potential analysis based on positive and negative surfaces.
From the secondary structure topology analysis, we noticed nine antiparallel β-sheets forming β-
sheets topology and five hairpins were involved in forming the secondary structure.
Conclusion: Our inferences from this study would be helpful in understanding the structure–function
relationships of LMTK3 and also help in designing suitable inhibitors for LMTK3.