GENESIS (Generalized‐Ensemble Simulation System) is a new software package for molecular dynamics ( MD ) simulations of macromolecules. It has two simulators, called ATDYN and SPDYN . parallelized based on an atomic decomposition algorithm the all‐atom force‐field models as well coarse‐grained Go‐like models. highly domain scheme, allowing large‐scale supercomputers. Hybrid schemes combining OpenMP MPI are used in both simulators to target modern multicore computer architectures. Key...

GENeralized-Ensemble SImulation System (GENESIS) is a software package for molecular dynamics (MD) simulation of biological systems. It designed to extend limitations in system size and accessible time scale by adopting highly parallelized schemes enhanced conformational sampling algorithms. In this new version, GENESIS 1.1, functions advanced algorithms have been added. The all-atom coarse-grained potential energy used AMBER GROMACS packages now become available addition CHARMM functions....

The growing interest in the complexity of biological interactions is continuously driving need to increase system size biophysical simulations, requiring not only powerful and advanced hardware but adaptable software that can accommodate a large number atoms interacting through complex forcefields. To address this, we developed implemented strategies GENESIS molecular dynamics package designed for numbers processors. Long-range electrostatic were parallelized by minimizing processes involved...

The ongoing COVID-19 pandemic caused by the new coronavirus, SARS-CoV-2, calls for urgent developments of vaccines and antiviral drugs. spike protein SARS-CoV-2 (S-protein), which consists trimeric polypeptide chains with glycosylated residues on surface, triggers virus entry into a host cell. Extensive structural functional studies this have rapidly advanced our understanding S-protein structure at atomic resolutions, although most these overlook effect glycans attached to conformational...

Spike (S) protein is the primary antigenic target for neutralization and vaccine development severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It decorates virus surface undergoes large motions of its receptor binding domains (RBDs) to enter host cell. Here, we observe Down, one-Up, one-Open, two-Up-like structures in enhanced molecular dynamics simulations, characterize transition pathways via inter-domain interactions. Transient salt-bridges between RBDA RBDC interaction with...

Residue-level coarse-grained (CG) models have become one of the most popular tools in biomolecular simulations trade-off between modeling accuracy and computational efficiency. To investigate large-scale biological phenomena molecular dynamics (MD) with CG models, unified treatments proteins nucleic acids, as well efficient parallel computations, are indispensable. In GENESIS MD software, we implement several residue-level covering structure-based context-based potentials for both...

GENeralized-Ensemble SImulation System (GENESIS) is a molecular dynamics (MD) software developed to simulate the conformational of single biomolecule, as well interactions in large biomolecular assemblies and between multiple biomolecules cellular environments. To achieve latter purpose, earlier versions GENESIS emphasized high performance atomistic MD simulations on massively parallel supercomputers, with or without graphics processing units (GPUs). Here, we implemented multiscale that...

In this paper, we address high performance extreme-scale molecular dynamics (MD) algorithm in the GENESIS software to perform cellular-scale simulations with more than 100,000 CPU cores. It includes (1) new of real-space nonbonded interactions maximizing on ARM architecture, (2) reciprocal-space minimizing communicational cost, (3) accurate temperature/pressure evaluations that allows a large time step, and (4) effective parallel file inputs/outputs (I/O) for MD extremely huge systems. The...

Flexible fitting is a computational algorithm to derive new conformational model that conforms low-resolution experimental data by transforming known structure. A common application against from cryo-electron microscopy obtain models in functional states. The conventional flexible algorithms cannot correct structures some cases due the complexity of transitions. In this study, we show importance ensemble refinement process performing multiple fittings trials using variety different force...

Abstract F 1 -ATPase comprises the stator ring consisting of α₃β₃ subunits and rotor γ subunit. The subunit rotation mechanism has been extensively investigated by biochemical analyses, structural studies, single-molecule measurements, computational studies. Recent cryo-electron microscopy (cryo-EM) structures from thermophilic bacterium Bacillus PS3 (TF ) provide us with further possibilities for a better understanding γ-rotation mechanisms. Using cryo-EM having angles close to binding...

Quantum mechanics/molecular mechanics (QM/MM) calculations are applied for anharmonic vibrational analyses of biomolecules and solvated molecules. The QM/MM method is implemented into a molecular dynamics (MD) program, GENESIS, by interfacing with external electronic structure programs. Following the geometry optimization harmonic normal-mode analysis based on partial Hessian, potential energy surface (PES) generated from energies gradients calculated at grid points. PES used self-consistent...

In recent years, molecular dynamics (MD) simulations with larger time steps have been performed the hydrogen-mass-repartitioning (HMR) scheme, where mass of each hydrogen atom is increased to reduce high-frequency motion while a non-hydrogen bonded decreased keep total unchanged. Here, we optimize scaling factors in HMR and combine them previously developed accurate temperature/pressure evaluations. The heterogeneous are useful avoid structural instability amino acid residues having five- or...

The mechanism of proton transfer in ice is investigated theoretically by examining the potential energy surfaces and determining reaction coordinates. It found to be quite different from that liquid water. As shown many authors, water promoted structure fluctuation, creating three-coordinated molecules hydrogen bond network rearrangement, excess makes transitions among these as forming a so-called Zundel structure, (H5O2)+. This kind large structural rearrangement cannot take place ice....

Collective variables (CVs) are often used in molecular dynamics simulations based on enhanced sampling algorithms to investigate large conformational changes of a protein. The choice CVs these is essential because it affects simulation results and impacts the free-energy profile, minimum pathway (MFEP), transition-state structure. Here we examine how many required capture correct structure during open-to-close motion adenylate kinase using coarse-grained model mean forces string method...

The graphics processing unit (GPU) has become a popular computational platform for molecular dynamics (MD) simulations of biomolecules. A significant speedup in the small- or medium-size systems using only few computer nodes with single multiple GPUs been reported. Because GPU memory limitation and slow communication between on different nodes, it is not straightforward to accelerate MD large biological that contain million more atoms massively parallel supercomputers GPUs. In this study, we...

In molecular dynamics (MD) simulations, a proper definition of kinetic energy is essential for controlling pressure as well temperature in the isothermal-isobaric condition. The virial theorem provides an equation that connects average with product particle coordinate and force. this paper, we show satisfied MD simulations larger time step holonomic constraints bonds, only when used. We provide novel energy, which calculated from velocities at half-time steps (t − Δt/2 t + Δt/2) velocity...

Sarcoplasmic reticulum (SR) Ca2+-ATPase transports two Ca2+ ions from the cytoplasm to SR lumen against a large concentration gradient. X-ray crystallography has revealed atomic structures of protein before and after dissociation Ca2+, while biochemical studies have suggested existence intermediate states in transition between E1P⋅ADP⋅2Ca2+ E2P. Here, we explore pathway free energy profile using atomistic molecular dynamics simulations with mean-force string method umbrella sampling. The...

A proton attachment dynamics to a water cluster is investigated by using classical molecular calculation. It found that three dynamical stages are involved: (1) ultrafast (∼10−14 s) molecule of the which followed (2) fast (∼10−13 sequential transfer over several molecules on surface and then, (3) gradual (∼10−11 penetration core. In first two stages, large kinetic energy order hundreds kcal/mol released system, results in evaporation few from cluster. The evaporating these early have...

In molecular dynamics (MD) simulations, an accurate evaluation of temperature is essential for controlling as well pressure in the isothermal-isobaric conditions. According to Tolman's equipartition theorem, all motions particles should share a single temperature. However, conventional estimation from kinetic energy does not include Hessian terms properly, and thereby, theorem satisfied with large time step. this paper, we show how evaluate most accurately without increasing computational...

The mechanism of the excess-proton transfer in ice is investigated by analyzing potential energy surface, normal modes, and interaction between excess proton defects. It found that solvation from water molecules long-distance shells essential for smooth transport proton. up to, example, about 18th shell are needed to attain a convergence energies. surface calculated with including these distant hydration very even long distance transport. Normal modes along reaction paths transfer. An...

Adenosine triphosphate (ATP) is an indispensable energy source in cells. In a wide variety of biological phenomena like glycolysis, muscle contraction/relaxation, and active ion transport, chemical released from ATP hydrolysis converted to mechanical forces bring about large-scale conformational changes proteins. Investigation structure-function relationships these proteins by molecular dynamics (MD) simulations requires modeling solution bound with accurate force-field parameters. this...

The present work addresses the question of how electron tunneling matrix elements can be quantitatively calculated. In particular, we demonstrate to go beyond Pathways methods, which have been shown qualitatively appropriate do such calculations. Utilizing a combination molecular dynamics with semiempirical and ab initio (Hartree–Fock) quantum chemistry calculations, quantify quality electronic Hamiltonian affect outcome elements. We show that is dominated by either one or, at most, few...