A Direct, Quantitative Connection between Molecular Dynamics Simulations and Vibrational Probe Line Shapes.

Area of Science:

• Computational chemistry
• Biophysics
• Spectroscopy

Background:

• Bridging molecular dynamics (MD) simulations and vibrational spectroscopy is crucial for translating experimental data into structural and dynamical insights.
• Simulating vibrational probe spectroscopy requires accurate methods that capture nonelectrostatic interactions.

Purpose of the Study:

• To establish a quantitative link between MD simulations and vibrational spectroscopy for probe-labeled systems.
• To evaluate different computational approaches for simulating infrared probe line shapes.

Main Methods:

• All-atom molecular dynamics (MD) simulations of a calmodulin-target peptide complex with two SCN probe sites.
• Infrared probe line shape simulations using quantum mechanics/molecular mechanics (QM/MM) and solvatochromic fragment potential (SolEFP) methods.

Main Results:

• QM/MM simulations showed disagreement with experimental data.
• SolEFP simulations accurately reproduced experimental frequencies and line shapes.
• Identified exchange repulsion between the probe and local neighbors as the primary determinant of CN probe frequency.
• Provided a dynamic explanation for the broad probe line shape at the buried site.

Conclusions:

• The SolEFP approach offers a reliable method for simulating vibrational probe spectroscopy.
• This methodology enables direct interpretation of experimental vibrational spectroscopy data using MD simulations.
• The approach is broadly applicable to various vibrational probes in diverse environments.