Pang, Yui Tik Miao, Yinglong Wang, Yi McCammon, J Andrew Gaussian Accelerated Molecular Dynamics in NAMD. GaMD implemented in the scalable NAMD is widely applicable to enhanced sampling and free energy calculations of large biomolecules. The reweighted free energy profiles are used to characterize the protein folding and ligand binding pathways quantitatively. Further GaMD simulations have captured folding of the chignolin and binding of the acetylcholine (ACh) endogenous agonist to the M3 muscarinic receptor. For alanine dipeptide, while conventional molecular dynamics (cMD) simulations performed for 30 ns are poorly converged, GaMD simulations of the same length yield free energy profiles that agree quantitatively with those of 1000 ns cMD simulation.

Here, we have implemented GaMD in the NAMD package on top of the existing aMD feature and validated it on three model systems: alanine dipeptide, the chignolin fast-folding protein, and the M3 muscarinic G protein-coupled receptor (GPCR). Taken together, GaMD offers major advantages for both unconstrained enhanced sampling and free energy calculations of large biomolecules. Furthermore, because the boost potential is constructed using a harmonic function that follows Gaussian distribution in GaMD, cumulant expansion to the second order can be applied to recover the original free energy profiles of proteins and other large biomolecules, which solves a long-standing energetic reweighting problem of the previous aMD method. Like the previous accelerated molecular dynamics (aMD), GaMD allows for â€œunconstrainedâ€ enhanced sampling without the need to set predefined collective variables and so is useful for studying complex biomolecular conformational changes such as protein folding and ligand binding. Gaussian accelerated molecular dynamics (GaMD) is a recently developed enhanced sampling technique that provides efficient free energy calculations of biomolecules. Gaussian Accelerated Molecular Dynamics in NAMD

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