Comparison of Implicit and Explicit Solvation Models for Iota-Cyclodextrin Conformation Analysis from Replica...

Area of Science:

• * Supramolecular Chemistry
• * Computational Chemistry
• * Drug Delivery Systems

Background:

• * Large ring cyclodextrins are crucial for drug delivery.
• * Understanding iota-cyclodextrin (CD14) conformational diversity is key for optimizing its applications.
• * Previous studies lacked detailed conformational analysis of CD14.

Purpose of the Study:

• * To investigate the conformational landscape of iota-cyclodextrin (CD14) using molecular dynamics simulations.
• * To evaluate the impact of implicit and explicit water solvation models on CD14 conformation.
• * To develop novel quantitative methods for analyzing molecular conformations.

Main Methods:

• * Replica-exchange molecular dynamics simulations were employed.
• * Both implicit (GB Igb5) and explicit (TIP3P) water solvation models were utilized.
• * New methods analyzing circularity, biplanar angle, and one-directional conformation (ODC) were developed and applied.
• * Gaussian Mixture Model (GMM) clustering was used for conformation classification.

Main Results:

• * CD14 in implicit water (Igb5) predominantly adopts an open conformation (avg. circularity 0.39 ± 0.16).
• * CD14 in explicit water (TIP3P) shows a significantly twisted conformation (avg. circularity 0.16 ± 0.10), with 29.1% being ODCs.
• * GMM analysis revealed 85.0% elliptical conformations in implicit water vs. 82.3% twisted conformations in explicit water.
• * Minority conformations including 8-shape and boat-form were identified.

Conclusions:

• * Solvation models profoundly affect iota-cyclodextrin (CD14) conformational preferences.
• * The study introduces new, quantifiable methods for analyzing complex molecular shapes.
• * Findings provide crucial insights for designing CD14-based drug delivery systems.