AMBERff at scale: multimillion-atom simulations with AMBER force fields in NAMD
Date
2022
Authors
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Publisher
University of Delaware
Abstract
All-atom molecular dynamics (MD) simulations are an essential structural biology technique with a demonstrated record of groundbreaking biological discoveries. The application of MD simulations to study large-scale biomolecular systems containing millions of atoms can reveal incredible details about viral and cellular processes that are inaccessible to experimental methods. Classical MD simulations rely on "force fields" carefully parameterized for each class of biomolecule to accurately describe molecular motion. Importantly, the AMBER family of force fields (AMBERff) includes a more accurate and extensively validated description of nucleic acids. Yet, it is not currently tractable to use AMBERff for multimillion-atom simulations, the minimum scale required to study the activity and emergent properties of biologically-relevant systems. To address this, the authors take advantage of the direct cancellation between the potential energy functions to refactor several popular force fields within AMBERff into the CHARMM file format. These refactored files are compatible with the freely-available NAMD software, which supports MD simulations of biomolecular systems up to two billion atoms on leadership-class supercomputers. Direct comparison of the single point energies for a comprehensive set of test systems show that this process preserves the integrity of the AMBERff force fields. Further, case studies using wellcharacterized biological systems show that these refactored files faithfully reproduce a number of biophysical properties across several classes of biomolecules. Implementation of AMBERff for NAMD will enable application of the leading nucleic acid force field for investigation of viral and cellular processes that involve genome.
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Keywords
AMBER, CHARMM, Force fields, Molecular dynamics, NAMD, Simulation