On computing the solubility of molecular systems subject to constraints using the extended Einstein crystal method

Area of Science:

• Computational Chemistry
• Molecular Modeling
• Physical Chemistry

Background:

• Atomistic simulations are crucial for predicting molecular solubilities.
• The Einstein crystal method offers a promising approach for solubility calculations.
• Holonomic molecular constraints are common in practical simulations but pose theoretical challenges.

Purpose of the Study:

• To investigate the applicability of an extended Einstein crystal method for systems with holonomic molecular constraints.
• To demonstrate that the derived mathematical relation for solubility calculation remains valid despite constraints.

Main Methods:

• Utilized an extension of the Einstein crystal method for atomistic simulations.
• Analyzed the mathematical derivation of the partition function factorization under holonomic constraints.
• Applied the methodology to systems featuring molecular constraints.

Main Results:

• The mathematical relation for solubility calculation, derived from partition function factorization, is applicable even for systems with holonomic constraints.
• A slightly modified mathematical procedure is required, but the core relation holds.
• This extends the utility of the method to a wider range of practical molecular simulations.

Conclusions:

• The extended Einstein crystal method is robust and applicable for computing solubilities in molecular systems with holonomic constraints.
• This work broadens the scope of atomistic simulations for solubility prediction, particularly for challenging pharmaceutical molecules.
• The findings facilitate more accurate solubility predictions in drug development and materials science.