Exact Analytical Algorithm for the Solvent-Accessible Surface Area and Derivatives in Implicit Solvent Molecular...

Area of Science:

• Computational chemistry
• Molecular modeling
• Biophysics

Background:

• Accurate calculation of solvent-accessible surface area (SASA) is crucial for molecular dynamics (MD) simulations.
• Existing numerical methods for SASA calculation can be computationally intensive and may lack analytical derivatives.

Purpose of the Study:

• To present differentiable solvent-accessible surface area (dSASA), an exact geometric method for analytical SASA calculation with derivatives.
• To implement dSASA on Graphics Processing Units (GPUs) for accelerated computations.
• To integrate dSASA into molecular dynamics simulations for improved accuracy and efficiency.

Main Methods:

• Delaunay tetrahedralization for assigning atoms into groups.
• Inclusion-exclusion principle for SASA calculation.
• GPU implementation for high-performance computing.
• Integration into AMBER for molecular dynamics simulations.

Main Results:

• dSASA achieves >98% accuracy compared to numerical icosahedral-based methods for proteins and RNAs.
• GPU-accelerated GB/SA simulations show up to 20-fold speedup over CPU versions.
• dSASA outperforms the LCPO algorithm in speed as system size increases.
• Stable GB/SA MD simulations were demonstrated for mini-proteins.

Conclusions:

• dSASA provides an accurate and efficient method for calculating SASA and its derivatives.
• GPU acceleration significantly enhances the performance of implicit solvent MD simulations.
• dSASA is a valuable tool for molecular modeling, particularly for large biomolecules and complex simulations.