scholarly journals An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems

2021 ◽  
Author(s):  
Fréderic Célerse ◽  
Theo Jaffrelot-Inizan ◽  
Louis Lagardère ◽  
Olivier Adjoua ◽  
Pierre Monmarché ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Adaptive Sampling ◽  
Sampling Strategy ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Enhanced Sampling ◽  
Polarizable Force Field ◽  
Accelerated Molecular Dynamics ◽  
Polarizable Force Fields ◽  
Multi Level

We detail a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We then introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual-water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2-CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS--GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD--US and US.

An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems

2021 ◽  
Author(s):  
Fréderic Célerse ◽  
Theo Jaffrelot-Inizan ◽  
Louis Lagardère ◽  
Olivier Adjoua ◽  
Pierre Monmarché ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Adaptive Sampling ◽  
Sampling Strategy ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Enhanced Sampling ◽  
Polarizable Force Field ◽  
Accelerated Molecular Dynamics ◽  
Polarizable Force Fields ◽  
Multi Level

We detail a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We then introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual-water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2-CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS--GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD--US and US.

scholarly journals An Efficient GaMD Multi-Level Enhanced Sampling Strategy for Polarizable Force Fields Simulations of Large Biological Systems

2021 ◽  
Author(s):  
Fréderic Célerse ◽  
Theo Jaffrelot-Inizan ◽  
Louis Lagardère ◽  
Olivier Adjoua ◽  
Pierre Monmarché ◽  
...  
Keyword(s):  
Adaptive Sampling ◽  
Sampling Strategy ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Enhanced Sampling ◽  
Polarizable Force Field ◽  
Accelerated Molecular Dynamics ◽  
Polarizable Force Fields ◽  
Solute Interactions ◽  
Multi Level

We introduce a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs -accelerated implementation within Tinker-HP. For the specific use with the flexible AMOEBA polarizable force field (PFF), we introduce the new "dual–water" GaMD mode. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups with fast multiple–timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual–water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2–CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS–GaMD capabilities but also the introduction of the new Adaptive Sampling–US–GaMD (ASUS–GaMD) scheme. The highly parallel ASUS–GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD–US and US.

scholarly journals An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems

2021 ◽  
Author(s):  
Fréderic Célerse ◽  
Theo Jaffrelot-Inizan ◽  
Louis Lagardère ◽  
Olivier Adjoua ◽  
Pierre Monmarché ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Adaptive Sampling ◽  
Force Fields ◽  
Biological Systems ◽  
Sampling Strategy ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Enhanced Sampling ◽  
Polarizable Force Fields ◽  
Multi Level

We introduce a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field.By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual--water approach is tested on the 1D Potential of Mean Force (PMF) of the solvated CD2--CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS-GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 times compared to GaMD-US and US. Overall, beside the acceleration of PMF computations, Tinker-HP now allows for the simultaneous use of Adaptive Sampling and GaMD-"dual water" enhanced sampling approaches increasing the applicability of polarizable force fields to large scale simulations of biological systems.

scholarly journals High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling

2021 ◽  
Author(s):  
Théo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Olivier Adjoua ◽  
Dina El Ahdab ◽  
Luc-Henri Jolly ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Adaptive Sampling ◽  
Force Fields ◽  
Sampling Strategy ◽  
Md Simulations ◽  
Conformational Space ◽  
Many Body ◽  
Polarizable Force Fields ◽  
Main Protease

We provide an unsupervised adaptive sampling strategy capable of producing μs-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs).

SPONGE : A GPU‐Accelerated Molecular Dynamics Package with Enhanced Sampling and AI‐Driven Algorithms

2021 ◽  
Author(s):  
Yu‐Peng Huang ◽  
Yijie Xia ◽  
Lijiang Yang ◽  
Jiachen Wei ◽  
Yi Isaac Yang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Enhanced Sampling ◽  
Accelerated Molecular Dynamics

scholarly journals Identification of rare Lewis oligosaccharide conformers in aqueous solution using enhanced sampling molecular dynamics

2017 ◽  
Author(s):  
Irfan Alibay ◽  
Kepa K. Burusco ◽  
Neil J. Bruce ◽  
Richard A. Bryce
Keyword(s):  
Molecular Dynamics ◽  
Aqueous Solution ◽  
Md Simulations ◽  
Umbrella Sampling ◽  
Biological Action ◽  
Sialyl Lewis X ◽  
Enhanced Sampling ◽  
Sialyl Lewis ◽  
Aqueous Solvent ◽  
A Minor

<p>Determining the conformations accessible to carbohydrate ligands in aqueous solution is important for understanding their biological action. In this work, we evaluate the conformational free energy surfaces of Lewis oligosaccharides in explicit aqueous solvent using a multidimensional variant of the swarm-enhanced sampling molecular dynamics (msesMD) method; we compare with multi-microsecond unbiased MD simulations, umbrella sampling and accelerated MD approaches. For the sialyl Lewis A tetrasaccharide, msesMD simulations in aqueous solution predict conformer landscapes in general agreement with the other biased methods and with triplicate unbiased 10 ms trajectories; these simulations find a predominance of closed conformer and a range of low occupancy open forms. The msesMD simulations also suggest closed-to-open transitions in the tetrasaccharide are facilitated by changes in ring puckering of its GlcNAc residue away from the <sup>4</sup>C<sub>1</sub> form, in line with previous work. For sialyl Lewis X tetrasaccharide, msesMD simulations predict a minor population of an open form in solution, corresponding to a rare lectin-bound pose observed crystallographically. Overall, from comparison with biased MD calculations, we find that triplicate 10 ms unbiased MD simulations may not be enough to fully sample glycan conformations in aqueous solution. However, the computational efficiency and intuitive approach of the msesMD method suggest potential for its application in glycomics as a tool for analysis of oligosaccharide conformation.</p>

Temperature Accelerated Molecular Dynamics with Soft-Ratcheting Criterion Orients Enhanced Sampling by Low-Resolution Information

2015 ◽  
Vol 11 (7) ◽  
pp. 3446-3454 ◽  
Author(s):  
Isidro Cortes-Ciriano ◽  
Guillaume Bouvier ◽  
Michael Nilges ◽  
Luca Maragliano ◽  
Thérèse E. Malliavin
Keyword(s):  
Molecular Dynamics ◽  
Enhanced Sampling ◽  
Low Resolution ◽  
Accelerated Molecular Dynamics

scholarly journals Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem

2019 ◽  
Vol 20 (17) ◽  
pp. 4268
Author(s):  
Chetna Tyagi ◽  
Tamás Marik ◽  
Csaba Vágvölgyi ◽  
László Kredics ◽  
Ferenc Ötvös
Keyword(s):  
Molecular Dynamics ◽  
Enhanced Sampling ◽  
New Approach ◽  
E Coli ◽  
Accelerated Molecular Dynamics ◽  
Simulation Techniques ◽  
Unfolded State ◽  
Folding Dynamics ◽  
Transmembrane Channels ◽  
Dynamics Simulations

The use of enhanced sampling molecular dynamics simulations to facilitate the folding of proteins is a relatively new approach which has quickly gained momentum in recent years. Accelerated molecular dynamics (aMD) can elucidate the dynamic path from the unfolded state to the near-native state, “flattened” by introducing a non-negative boost to the potential. Alamethicin F30/3 (Alm F30/3), chosen in this study, belongs to the class of peptaibols that are 7–20 residue long, non-ribosomally synthesized, amphipathic molecules that show interesting membrane perturbing activity. The recent studies undertaken on the Alm molecules and their transmembrane channels have been reviewed. Three consecutive simulations of ~900 ns each were carried out where N-terminal folding could be observed within the first 100 ns, while C-terminal folding could only be achieved almost after 800 ns. It took ~1 μs to attain the near-native conformation with stronger potential boost which may take several μs worth of classical MD to produce the same results. The Alm F30/3 hexamer channel was also simulated in an E. coli mimicking membrane under an external electric field that correlates with previous experiments. It can be concluded that aMD simulation techniques are suited to elucidate peptaibol structures and to understand their folding dynamics.

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