GENESIS Hands-on
Part 1: GENESIS basics and GENESIS onFugaku- Lecture Chigusa Kobayashi
RIKEN Center for Computational Science
2024/06/30
IUPAB2024 Hands-on Training Program CHARMM-GUI/GENESIS MD Tutorial
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Schedule of GENESIS parts (6/30-7/2)
06/30 Part1
13:30 – 15:00

GENESIS basics and GENESIS on Fugaku (Kobayashi)
LectureHands-on tutorial on Fugaku

07/01 Part 2
14:30 – 15:30

Coarse-grained simulations in GENESIS (Tan)

15:30 – 16:30

High-performance computation with GENESIS (Jung)

07/02 Part 3
13:30 – 15:00

Generalized-ensemble simulations using GENESIS (Ito)2

Contents• Molecular Dynamics (MD)• MD software, GENESIS• What we can do by using GENESIS

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Molecular Dynamics (MD)- calculates motion of particles based on the Newtonʼs equation of motion.

𝑑𝐫𝑑𝑡
𝑑𝐩
𝑑𝑡

𝐩𝑚
𝐅

Equation of motion

𝐫 𝑡Δ𝑡𝐫 𝑡

𝐩 𝑡

Δ𝑡

𝐩 𝑡

𝐩Δ𝑡
𝑚
𝐅 Δ𝑡

Integration

Motions of particles

Fi : force of i-th particle
ri : coordinate of i-th particle
pi : momentum of i-th particle
mi : atomic mass of i-th particlet : time
Dt : timestep size
4Procedure of MDIn MD, numerical integration is repeated with a small timestep.
Very simplified procedure
Initialization (m, r, p)
Bottleneck!
Calculate force (F)Update coordinates/momenta (r, p)

Repeating procedure;
To get 1 ms trajectory, asimulation with 5×1011
steps is required.

Update thermostat/barostat
Finish?

NoUpdate time(t → t+t)

Yes5

Force calculation for biological systems
Force can be divided into bonding and nonbonding interactions.
Etotal  kb (b  b0 )2

Bond (ex. 1-2, 2-3, …)

bonds
13245Hydrogen: Light Gray
Carbon: Dark Gray
Oxygen: RedNitrogen: Blue…

 ka (  0 )2Angle (ex. 1-2-3, 2-3-4,..)

BondingO(N)angles Vn [1  cos(n   )] Dihedral (ex. 1-2-3-4, …)dihedrals

126
 


rrqq0ij  0ij
 i j


2




  ij  r 


r
rij 
 ij  i , jbonding   ij van der Waals(ex. 1-5, …) :Nonbonding
O(N2)Coulomb(ex. 1-5, …) :6

Nonbonded interactions• Nonbonded interactions (Coulomb + vdW) are the main bottleneck of simulations.
• Nonbonded interactions are divided into those of real spacewith cutoff-distance and reciprocal lattice space.

All pairs
O(N2)Pairs within cutoff-distance + Long-range interactions
O(CN)
126
 
 r0ij  qqerfc(r)exp(k 2 / 4 2 )ijij  r0ij FFT(Q(k ))  2
 f (r )  ij  2 rij   ijrrkijij rij  R &i , jbonding   k 0

Real space, O(CN)

Reciprocal space, O(NlogN)

Darden et al., J. Chem. Phys., 98, 10089-10092 (1993).
Essmann et al., J. Chem. Phys., 103, 8577-8593 (1995).

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History of molecular dynamics (MD) simulation
psns

vibration

msms

BPTI 4, Ubiquitin 5(~2x104)

AQP13(~105)

Proteincomplex(# of atoms) size

HP362(~104)

2000

Membraneprotein

Cellularscale
simulation

Reaction in Protein

BPTI 1
1977 (~6x102)

Protein insolvent

2013

Ribosome6(~2x106)
HIV-1 capsid7(~6.5x107)
Mycoplasma
genitalium8(~1.0x108)

LANL

Chromatin10(~1.0x109)

time

Protein Folding

relaxation

secondary structural change
ProteinsANTON(Gordon Bell Prize 2009)

To investigate biological systems,
a single MD simulation is notenough.

HIV-1 capsid9(~6.5x107)~2019
Chromatophore
vesicle111.
2.
(~1.4x108)
3.
4.
5.
6.
7.

Extensive simulation
methods are required!
Nature,267,585(1977)
Science,282,740 (1998)
Science,294, 2353 (2001)
Science,330, 341 (2010)
PNAS,110,5915 (2013)
PLOS Comput. Biol.,9, e1003003 (2013)
Nature, 497, 643 (2013)

8.
9.
10.
11.

eLife, 5, e19274 (2016)
Nat. Comm. 8,15959 (2017)
J. Comp. Chem., 40, 1919 (2019)
Cell, 5, 1098(2019)8

Contents• Molecular Dynamics (MD)• MD software, GENESIS• What we can do by using GENESIS

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Generalized Ensemble Simulation Systems (GENESIS)•MD software developed in RIKEN from 2009https://www.r-ccs.riken.jp/labs/cbrt/

Version 1.0: Jung, Mori, et al. WIREs Comput. Mol. Sci. 5:310-323,(2015)
Version 1.1.x: Kobayashi, Jung, et al. J. Comput. Chem. 38, 21932206 (2017)
Version 2.x : Jung, Yagi, Tan, et al. J. Phys. Chem. B 128, 60286048 (2024)

Please find the website by search engine, “GENESIS RIKEN”.
•Free software under LGPLv3•Two key features:•High performance in large-scale biomolecular simulations.

•

Efficient conformational sampling based on various multi-copy methods.

•→ Take the advantage of high performances of supercomputers

10Key features
High performance

Efficient conformational sampling methods

GPU→ 2nd day (Jung)→ 3rd day (Ito)Enable QM/MM, all-atom and coarse-grained models

QM/MMAll-atom (AA)Coarse grained (CG)→ Today→ 2nd day (Tan)Performance of AA model on Fugaku

Jung et al. J. Comput. Chem. 42, 231-240(2021) https://doi.org/10.1002/jcc.26450

4 times better
performance than
GENESIS1.0 on K using
1/8 nodes
11.9 ns/day

12Performance of CG model on Fugaku
Jung et al. Nat. Commun. 15, 3370 (2024).

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Efficient conformational sampling methods
Sampling methods in GENESIS have been applied to various biological systems.
gREST
Kamiya and Sugita, J. Chem. Phys. 149,072304 (2018)

S-protein on surfaceof CoV-19

Dokainish et al., eLife, 11, e75720 (2022)

gREST/REUS

String method

REMD : Sugita and Okamoto, Chem. Phys. Lett. 314, 141-151 (1999) Maragliano et al., J. Chem. Phys. 125, 024106 (2006)
REUS : Sugita et al., J. Chem. Phys. 113, 6042-6051 (2000)

Kinase-inhibitor binding

Conformational changes ofCa2+-ATPase

Re et al. PNAS, 116 18404-18409(2019)

Kobayashi et al., PNAS, 118, e2105507118 (2021)… and there's more!

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Enable multiple models
Various models with different resolutions are available in GENESIS.

From GENESIS manualAA FFs
CG models
Force fields: CHARMM/CHARMM19/AMBER/MARTINI/Ca GO/All-atom GO/RESIDCGFor QM/MM : the following QM software can be used.
••••

Gaussian09/Gaussian16(http://gaussian.com)
Q-Chem (http://www.q-chem.com)
TeraChem (http://www.petachem.com)
DFTB+ (https://www.dftbplus.org)•Qsimulate(https://qsimulate.com/academic)

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Contents• Molecular Dynamics (MD)• MD software, GENESIS• What we can do by using GENESIS

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Which machines we can execute GENESIS?
GENESIS can work on various machines!
Operating systems

Hardware• Linux• Mac OSX• Windows 10, 11 (spdyn, ver > 1.7.1)

Fortran and C compilers• IntelⓇ Xeon Ⓡ (> SSE4.2), Xeon Phi Ⓡ• AMD EPYCTM• ARM (Armv8.2-A SVE)
• NVIDIA GPU (CC >= 3.5)

• GCC compiler: gfortran, gcc (version > 7.0)
• Intel compiler: ifort, icc• Fujitsu compiler: frtpx, fccpx• Cygwin/mingw (spdyn, ver > 1.7.1)

Supercomputers• Fugaku (RIKEN)• Flow (Nagoya)• TSUBAME3.0 (Tokyo Tech.)• Cygnus (Tsukuba)• Oakbridge-CX (Tokyo)
etc17

What we can do by using GENESIS? (1)We have two MD applications; atdyn and spdyn.

• ATDYN : Many models (QM/MM, AA, CG) & readable codes CG, QM/MM, Cryo-EM• SPDYN : High performance
Basic, enhanced-sampling18

What we can do by using GENESIS? (2)We can analyze trajectories in GENESIS.
Most tools can execute on desktop and laptop;

Today (Kobayashi)
3 rd day (Ito)•Distance/angle/dihedral angles : trj_analysis•

RMSD: rmsd_analysis•Conversion of trajectory files : crd_convert, remd_convert•

PCA: avecrd_analysis, flccrd_analysis, eigmat_analysis, prjcrd_analysis(avecrd_analysis, flccrd_analysis can be used to RMSF）•Free energy calculation: mbar_analysis, wham_analysis, pmf_analysis …

•

Diffusion: msd_analysis, diffusion_analysis•

Lipid properties: lipidthink_analysis, tilt_analysis
Highlighted tools will be shown in hands-on
19What we can do by using GENESIS? (3)Modeling with coarse grained model can be done in GENESIS.
2 nd day (Tan)

GENESIS CG tools
Tan et al., PLoS Comp. Biol. 18, e1009578 (2022)

https://github.com/genesis-release-r-ccs/genesis_cg_tool20Tutorial of GENESIS (1)Please find “Tutorial and Samples” in our website.
Computer resources(Level1-3)

https://www.r-ccs.riken.jp/labs/cbrt/tutorials2022/
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Tutorial of GENESIS (2)We can find how to setup MD inputs in the tutorial site.
Setup by vmd1
(CHARMM FF: Soluble protein, DNA-protein)(skip)

Setup by AmberTools2(AMBER FF : Soluble protein, DNA-protein)
Setup by Gromacs tool3(AMBER FF : Soluble protein, DNA-protein)
Setup by CHARMM-GUI4(CHARMM FF︓Lipid bilayers,membrane protein, N-glycan)
1. https://www.ks.uiuc.edu/Research/vmd/
2. http://ambermd.org/AmberTools.php
3. https://www.gromacs.org/
4. https://www.charmm-gui.org/

Please check the license issue by yourselves.22

Summary• GENESIS - is MD software for biomolecule system.
- has three key features ;• High performance.
• Efficient sampling methods.
• Available QM/MM, all-atom, and coarse-grained models.
- includes two MD applications and more than 30 analysis tools.
• You can find how to use GENESIS in the GENESIS website.
Please enjoy this tutorial!
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