|
Keywords
|
Molecular dynamic simulation, Teriparatide (TPTD), Aggregation, Drug concentration, Cluster
analysis, Molecular-level investigation
|
|
Abstract
|
Teriparatide (TPTD), a recombinant peptide used in osteoporosis treatment, exhibits self-association
that may lead to immunogenicity and reduced therapeutic efficacy. To investigate its aggregation
behavior, we performed molecular dynamics simulations of systems containing 1, 5, and 10 TPTD
molecules in water, assessing concentration-dependent effects. Structural and dynamic properties
were analyzed using root-mean-square deviation, free energy landscapes, secondary structure
probabilities, and Kirkwood–Buff integrals derived from radial distribution functions. The simulations
reveal key intermolecular interactions and conformational preferences that drive TPTD self-assembly.
Water-mediated hydrogen bonding and hydrophobic contacts were found to modulate aggregation,
with notable structural compaction at higher concentrations. These findings provide mechanistic
insight into TPTD aggregation and offer guidance for minimizing immunogenic risks in peptide-based
therapeutics.
|