Overcoming potential energy distortions in constrained internal coordinate molecular dynamics simulations

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Biophysics

Background:

• Internal Coordinate Molecular Dynamics (ICMD) is valuable for simulating large bonded systems like proteins.
• ICMD allows hierarchical modeling, simplifying complex dynamics through torsional or rigid-body approaches.
• Standard ICMD methods can distort the potential energy landscape due to constraints.

Purpose of the Study:

• To address potential energy landscape distortions in constrained ICMD simulations.
• To improve the accuracy of molecular dynamics simulations for proteins and peptides.
• To present a two-part solution for mitigating distortions in ICMD.

Main Methods:

• Utilized the Fixman compensating potential to correct intrinsic distortions in torsional molecular dynamics.
• Developed a hybrid ICMD method for selective relaxation of bond angles, addressing extrinsic distortions.
• Applied these methods to peptide molecules to validate their effectiveness.

Main Results:

• The Fixman potential alleviates distortions arising from reduced phase space in torsional dynamics.
• The hybrid ICMD method effectively corrects distortions caused by coupling between dihedral and bond angles.
• Combined methods successfully eliminate potential energy distortions in constrained ICMD simulations.

Conclusions:

• The proposed methods (Fixman potential and hybrid ICMD) provide a robust solution for accurate ICMD simulations.
• These techniques bridge the gap between all-atom and torsional molecular dynamics.
• Enables more reliable large-scale conformational sampling and energy calculations for biomolecules.