Absolute and relative entropies from computer simulation with applications to ligand binding.

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Statistical Thermodynamics

Background:

• Calculating absolute molecular entropies is crucial for understanding chemical processes.
• Existing methods like Schlitter's formula have limitations in accuracy.
• Molecular dynamics (MD) simulations offer a powerful tool for thermodynamic calculations.

Purpose of the Study:

• To compare Schlitter's formula and quasiharmonic analysis for calculating absolute entropies from MD simulations.
• To develop and validate new methods for estimating translational and rotational entropies.
• To apply these methods to a biologically relevant system, the binding of benzene to T4-lysozyme.

Main Methods:

• Utilized molecular dynamics (MD) simulations to generate atomic fluctuation data.
• Applied Schlitter's formula and quasiharmonic analysis to calculate absolute entropies.
• Developed a novel method for rotational entropy using Euler angle variances.
• Investigated translational entropy estimation via center-of-mass root-mean-square (rms) fluctuations.

Main Results:

• Quasiharmonic analysis showed better agreement for vibrational entropies than Schlitter's formula.
• Both standard methods failed to accurately reproduce theoretical rotational entropies.
• The proposed Euler angle variance method yielded good agreement for rotational entropies.
• Alternative translational entropy methods based on rms fluctuations performed well.
• Successful application to benzene-T4-lysozyme binding, matching literature values.

Conclusions:

• Quasiharmonic analysis is a more reliable method for vibrational entropy calculations from MD.
• A new Euler angle-based approach improves rotational entropy estimation.
• MD simulations combined with refined methods provide accurate entropy calculations.
• These validated methods enhance the study of molecular interactions and binding affinities.