An explicit-solvent conformation search method using open software.

Area of Science:

• Computational chemistry
• Molecular modeling
• Drug discovery

Background:

• Conformational analysis is crucial for understanding molecular behavior.
• Existing methods often neglect explicit solvent effects, limiting accuracy.
• Solvent interactions significantly influence molecular stability and conformation.

Purpose of the Study:

• To develop and validate a computational workflow for conformational searches in explicit solvents.
• To enable more accurate prediction of molecular conformations by including solvent effects.
• To compare conformational preferences across gas, implicit, and explicit solvent models.

Main Methods:

• Utilized replica exchange molecular dynamics (REMD) for efficient conformational sampling.
• Employed cluster analysis to identify dominant conformations from simulation trajectories.
• Developed a workflow using open-source software for accessibility.

Main Results:

• Demonstrated a workflow for conformational searches on explicitly-solvated molecules.
• Showcased the method's effectiveness on drug molecules α-amanitin and cabergoline.
• Confirmed significant differences in preferred conformations between gas, implicit, and explicit solvent environments.

Conclusions:

• The developed workflow accurately models molecular conformations in explicit solvents.
• Explicit solvent modeling is essential for precise conformational analysis of drug molecules.
• This approach enhances the reliability of molecular modeling in pharmaceutical research.