myPresto 5.0

USER’S MANUAL
26th Sep 2018

Copyright (C) 2006-2018 Next Generation Natural Product Chemistry (N2PC)

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Program license agreement condition
See the attachment.

About copyrightThe copyright notice is as follows, unless otherwise noted.

Copyright indication as follows.
myPresto version 5.0 :Copyright (C) 2006-2018 Next Generation Natural Product Chemistry (N2PC)

myPresto 5.0

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ACKNOWLEDGEMENTS:
This work was supported by grants from New Energy and Industrial Technology Development
Organization (NEDO) and Ministry of Economy, Trade and Industry (METI), JAPAN. Part of the
Version 5.0 has also been supported by Japan Agency for Medical Research and Development(AMED). In addition, the program development was partly supported by Fujifilm Holding
Corporation, Japan Tobacco Inc., and Takeda Science Foundation.
This software was originally developed as part of a research project advanced by late Dr. Yoshimasa
Kyogoku.
The Particle Mesh Ewald (PME) routines were originally developed by Dr. Tom Darden [28].
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
US.
The Accessible Surface Area(ASA) routines were originally developed Dr. Akira R. Kinjo[40].
Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics,
Mishima, Shizuoka, 411-8540, Japan. He has been working at Institute for Protein Research, Osaka
University, 3-2 Yamadaoka, Suita, Osaka 565-0871, JapanThe Fast Multipole Method (FMM) routines were originally developed byDr. William T. Rankin.
Center for Computational Science and Engineering
Duke University
Dept. of Electrical and Computer Engineering, Box 90291, Durham, NC 27708-0291 US.

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Software authors•myPresto version 5

Nakamura, Haruki
Fukunishi, Yoshifumi
Mashimo, Tadaaki
Kurosawa, Takashi
Sugihara, Takanori
Wada, Mitsuhito
Higo, Junichi
Fukuda, Ikuo
Kawabata, Takeshi
Kamiya, Narutoshi
Kasahara, Kota
Bhaskar Dasgupta
Kanai, Chisato
Yoshikawa, Tatsuya
Sugihara, Yusuke
Nakamura, Hironori•myPresto version 4

Nakamura, Haruki
Fukunishi, Yoshifumi
Eiji, Kanamori
Kubota, Satoru
Omagari, Katsumi
Fukuda, Ikuo
Wada, Mitsuhito
Mashimo, Tadaaki
Mitomo, Daisuke
Sakamoto, Kuniko
Kurosawa, Takashi
Hashi, Yuichi
Mikami, Yoshiaki
Ueda, Hiroshi• myPresto version 3

Nakamura, Haruki
Fukunishi, Yoshifumi
Jae Gil Kim
Watanabe, Yukihisa S.
Mikami, Yoshiaki
Kubota, Satoru
Omagari, Katsumi
Tatsumi, Rie
Horie, Masaru
Fukuda, Ikuo

• myPresto version 2

Nakamura, Haruki
Fukunishi, Yoshifumi
Jae Gil Kim
Mikami, Yoshiaki
Watanabe, Yukihisa S.
Ina, Yasuo
Horie, Masaru
Takahashi, Makoto

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Fukuda, Ikuo

• myPresto version 1

cosgene version 1：
Nakamura, Haruki
Fukunishi, Yoshifumi
Hashi, Yuichi
Mikami, Yoshiaki
Kidera, Akinori
Terada, Toru
tplgene version 1：
Nakamura, Haruki
Fukunishi, Yoshifumi
Kuroda, Masataka
Fukuda, Ikuo

myPresto 5.0

viiTable of Contents
1. Overview and Characteristics of myPresto program package ..............................................1
1.1. Overview
1.2. Characteristics
2. Programs and Data Libraries for myPresto..............................................3

3. Access to obtain myPresto program package..............................................5

3.1. Download of myPresto program package..............................................5

3.2. Deployment of myPresto programs and data..............................................5

4. Computations available by myPresto program package..............................................6

4.1. Molecular Dynamics Simulation: cosgene..............................................6

4.2. Rapid Molecular Dynamics Simulation: psygene/psygene-G............................ 8

4.3. Docking Simulation: sievgene/sievgene_M..............................................94.4. in-silico Screening.............................................11

4.5. Search Similar Chemical Compounds : TGS.............................................13

4.6. Precise Docking: sievgene_NMR and MVO.............................................13

4.7. Estimate of Binding Free Energy: sievgene_DIAV.............................................13

4.8. Estimate of Precise Binding Free Energy: SRPG.............................................144.9. Prediction of Solubility and Aggregator: LogS_predictor
4.10. Search pockets from a protein surface: MolSite............................14.............................................14

4.11. 3D structure construction from 2D information of Chemical Compounds:
3DdataConstruction.............................................144.12. Editing Tool of Chemical Compounds: EditMol.............................................15

5. Tool Programs.............................................16

6. Configuration of Environment Variables.............................................17

7. List of Files to be Disseminated.............................................19

8. List of Documents.............................................20

9. References.............................................21

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1. Overview and Characteristics of myPresto program package
1.1. Overview
myPresto is a molecular simulation software system for drug development, supported by Ministry of
Economy, Trade and Industry, Japan (METI), New Energy and Industrial Technology Development
Organization (NEDO), and Japan Agency for Medical Research and Development (AMED). By
using this software, modeling of proteins with small chemical compounds, molecular dynamics
simulations for proteins with ligands in aqueous solutions or in membranes, and drug screening withdocking simulations are available much more effectively and quickly than before. The name of
myPresto comes from Medicinally Yielding PRotein Engineering SimulaTOr.
myPresto is a program suite, composed of many programs, libraries, and databases. The major
programs and database included in myPresto version 5.0 are as follows.
1) Creation of detailed information on molecules necessary for molecular simulation:“tplgeneX” for peptide chains and nucleic acids, and “tplgeneL” for small chemical compounds.
2) Molecular dynamics simulation programs:“cosgene” and “psygene”
3) Docking simulation:“sievgene”
4) Several tools:“Molsite” for pocket search, EditMol for molecular design, TGS for similar compounds search,
LogS_predictor for solubility prediction, SyntheticAccessibility for prediction of synthetic
accessibility.
5) Ligand database:“LigandBOX”

1.2. Characteristics
The characteristic features of myPresto program suite are as follows.
• Coordinated usage of molecular dynamics and docking simulations.
Both molecular dynamics (MD) and docking simulation programs have been developed
simultaneously, coordinated usages are designed. For example, results of an MD simulation(snapshot protein structures taken from trajectories of MD) can be easily used for drug docking. As
the inversed way, the complexed protein structure with the docked ligand molecule can be used as
the initial conformation for MD simulation. Many effective applications are available in myPresto,
using the coordinated usages of MD and docking simulations.

myPresto 4.0

2• Large-scale in-silico ligand screening
When the ligand database, “LigandBOX”, is used, large-scale in-silico ligand screening is easily
performed. Its purpose is to screen only the putative chemical compounds, the activities of which arethen examined experimentally, from huge number of the chemical compounds in the library.
There are two ways for in-silico screening. (1) Structure-Based Drug Screening (SBDS), baseson the 3-dimensional (3D) structure of the target protein receptor, and (2) Ligand-Based Drug
Screening (LBDS), based on the known ligand structures. myPresto can use both SBDS an LBDS.
• Tools for treating small chemical compounds
In myPresto program suite, many tools are prepared for actual works in drug development, such as“EditMol” for editing compounds, “LogS_predictor” for prediction of solubility of compounds, and“TGS” for similar compounds search.

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2. Programs and Data Libraries for myPresto
The following programs are included in myPresto suite:• myPresto Portal : Graphic user interface program for myPresto5• tplgeneX : Generation of molecular topology of a peptide and nucleic acids chains, and set theforce-field parameters of AMBER and CHARMm• tplgeneL : Generation of molecular topology of a chemical compound, and set force-fieldparameters of general AMBER force field (GAFF)• cosgene : Energy minimization and molecular dynamics (MD) simulation, with NVE/NVT/NPT
ensembles, SHAKE, rigid molecular mode, multicanonical MD (McMD), umbrella sampling, GBSA,SRPG for binding free energy computation• psygene : Rapid MD simulation with non-Ewald method and space decomposition algorithms.
GPU version is also available• Hgene : Addition of hydrogen atoms and atomic partial charges to chemical compounds• sievgene : Docking program of chemical compounds to a receptor protein• sievgene_NMR : Docking program of chemical compounds to a receptor protein, with NMR
experimental information• sievgene-MVO : Docking program of chemical compounds to a receptor protein, so that thecompounds overlap to the known ligand in the complexed structure• sievgene_DIAV : Docking program of chemical compounds to a receptor protein, where binding
free energy is estimated by a short MD trajectory of an apo-receptor protein.
• PDBcheck : Check a PDB file, process the N- and C-termini of the peptide chain, and identify theligands clearly.
• UAP : Selection of drug screening by Universal Active Probe (UAP) method• VCOL : Combinatorial generation of molecules• confgene/ confgeneC : A tool to generate molecular configurations• Matrix : in silico screening : Multiple Target Screening (MTS) method as SBDS, and Docking
Score Index (DSI) method as LBDS
• 3DdataConstruction : A tool to generate chemical compounds data for LigandBOX• MVO : Refinement of the docked structure by Maximum Volume Overlap (MBO) method• MVO_screening : Similar compounds search by MD-MVO method as LBDS
• substructure-search : Similar compounds search by molecular framework as LBDS
• TGS : Similar compounds search by TGS method as LBDS
• LogS_predictor: Prediction of solubility and aggregator by molecular descriptor andphysicochemical properties• MolSite : Search of ligand binding sites on the receptor protein by docking simulation• SyntheticAccessibility : Prediction of synthetic accessibility of chemical compounds

myPresto 5.0

4• mdmbgene : Modiling tool for a system including a transmembrane protein and lipid bilayer

myPresto 5.0

53. Access to obtain myPresto program package
3.1. Download of myPresto program package
myPresto programs and data are available from the following web site.
URL of myPresto download site:
http:// myPresto5.jp

3.2. Deployment of myPresto programs and data
myPresto programs and data are provided as compressed files, which should be uncompressed by thenext command. Here, only LINUX system is assumed. Some programs work on the UNIX system on
Windows, using cygwin of MinGW, but they are not guaranteed% tar –xzvf (program)YYMMDD.tar.gz(YYMMDD means Year/Month/Date)“(program)” depends on the files to be downloaded.
Many compressed files of myPresto version 5.0 are prepared to be automatically deployed with thefollowing directory structure, after uncompressing the compressed files.
(program)YYMMDD/|-doc/| |- (program)_manual_v5.000_ja_YYMMDD.pdf| …
|-src/|-bin/… |- install.sh…
Manual and/or Tutorial files in PDF are installed in the “doc/”directory. Users can refer those forusage of the programs.
When bin/install.sh is executed, programs can be installed. In this case, compilers for programs
should be installed beforehand.
Some packages include scripts “test_*.sh” for test computations for programs.

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4. Computations available by myPresto program package
4.1. Molecular Dynamics Simulation: cosgene
A molecular dynamics simulation program for protein, DNA, chemical compound, andprotein-ligand complex. with AMBER and CHARMM force fields are available. Cosgene cancalculate NVE, NVT and NPT ensemble with various boundary conditions. In addition, cosgene cancalculate the generalized ensemble like multicanonical ensemble by our original algorithm:
Multicanonical MD (McMD). Cosgene can calculate the protein-compound binding free energy by
the filling potential method. The generalized ensemble method is useful to calculate the free energy
surface (SPRG).
(Fukunishi, Y., Mikami, Y., Nakamura, H. (2003) J. Phys. Chem. B. 107, 13201-13210)
An Example of the protein system is shown in Fig. 1, which is composed of a protein, a small
chemical compounds, water and ions. Main functions of the cosgene program are listed in Table 1.
In myPresto 5.0, a package for MD simulations is prepared as cosgene_packYYMMDD.tar.gz,
where “YYMMDD” indicates Year/Month/Day.
Parallel usage is also available by using MPI, as cosgene_MPI. In that case, the following“make” command should be used:% make cosgene_MPI

Fig.1. Example of the protein system, a target of cosgene, including a protein, a small chemicalcompounds, water and ions.

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Table 1. Main functions of cosgene
Function type

Description

Energy minimization

Steepest decent method, Steepest decent method with SHAKE,
Conjugate gradient method

MD calculation

Micro-Canonical, Canonical, Force-biased Multi-Canonical
Tsallis Dynamics

Integrator

Leap-frog (Verlet), Velocity Verlet, RESPA

Thermostat

Hoover-Evans Gaussian constraint, Nose-Hoover

BarostatAndersen, Parrinello-RahmanLong

distance

Direct summation, Direct summation & Cutoff,interaction

Ewald, Particle Mesh Ewald, Fast Multipole Method

Restraints methods

SHAKE, RATTLE, Rigid-body,
Position restraint, Distance restraint

Boundary conditions

Sphere, ellipsoid, periodic boundary conditions

myPresto 5.0

84.2. Rapid Molecular Dynamics Simulation: psygene/psygene-G
The progeam psygene (Protein dYnamics SimulatinG ENginE), was developed for rapid MD
simulations. psygene uses our original non-Ewald algorithm (Zero-Dipole summation method ) for
electrostatic interactions with the space decomposition algorithm. The GPU (Graphics Processing
Units) version is also available as psygene-G for a single and multiple GPUs.
(Mashimo, T., Fukunishi, Y., Kamiya, N., Takano, Y., Fukuda, I., Nakamura, H. (2013) J. Chem.
Theory Comput. 9, 5599-5609)
Table 2. Main functions of psygene/psygene-G
Function type

Description

Energy minimization

Steepest decent method, Conjugate gradient method

MD calculation

Micro-Canonical, Canonical, NPT(ensemble)
Integrator

Leap-frog (Verlet), Velocity Verlet

Thermostat

Berendsen, Hoover-Evans Gaussian constraint, Nose-Hoover

BarostatBerendsen

Long distanceDirect summation, Direct summation & Cutoff,interaction

Zero Dipole method

Restraints methods

SHAKE, Position restraint, Distance restraint

Boundary conditions

periodic boundary conditions

myPresto 5.0

94.3. Docking Simulation: sievgene/sievgene_M
Pprograms, sievgene (SIEVinG ENginE) and sievgene_M are protein-compound docking programsfor in-silico (virtual) drug screening and prediction of protein-ligand complex structure. Sievgene isa fast flexible docking program. On average, it can dock one compound to a target in 1 sec with highaccuracy (56% complex structures satisfy RMSD < 2A in a self-docking test) on usual PC. It is
designed for PC grid computing.
(Fukunishi, Y., Mikami, Y., Nakamura, H. (2005) J. Mol. Graph. Model. 24, 34-45)
There are two versions in sievgene: 1) sievgene_for_dockingpose, which can provide accurate
docking poses, and 2) sievgene_for_screening, which can make rapid computations.
sievgene_M is an improved version of sievgene_for_screening that improved computational
efficiency. The usage of sievgene_M is almost the same as sievgene, you can use the same input file.
sievgene_M has two versions: parallel processing version and serial processing version.
The parallel processing version of sievgene_M enables high-speed calculation by parallel
processing using many CPU cores simultaneously for one docking calculation. This is suitable forcalculation of computation objects that take a long time for one docking calculation, for example,
relatively large compounds that can take huge numbers of conformations.
Serial processing version of sievgene_M (in particular, this is called sievgene_M_serial) uses
only one CPU core for one docking calculation. This is particularly suitable for drug candidate
compound screening calculations targeting a large number of low molecular compounds (more than
1 million)
For example, if you are using a 20 core system, you can calculate a docking between a proteins
and a compounds using 20 cores simultaneously in one job. In the serial processing version, it ispossible to efficiently calculate 20 dockings of 20 pairs of proteins and compounds with 20 jobs
using one core for each job.
sievgene_M also works on a system with a many-core CPU (Intel Xeon Phi) where more than
50 cores are mounted on one CPU, and it can fully exploit its performance. For example, in a modelwith 60 cores in one CPU, it is possible to efficiently calculate one docking using 60 parallel
processes at the same time. sievgene_M is not a program dedicated to Intel Xeon Phi, it also works
well with many CPUs. Currently, compilation of sievgene_M requires a Intel compiler.
In order to execute a docking calculation, users should prepare the protein atomic coordinatesfile (PDB file) with the molecular topology file and a file identifying the docking site on the protein
surface. For those preparations, several tools, pdbcheck, tplgeneX, and make_point, are available.
All those programs are included in a program package: sievgene_packYYMMDD.tar.gz,
sievgene_M_packYYMMDD.tar.gz, where YYMMDD indicates Year/Month/Date.

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10Fig. 2. Example of ligand docking to a protein by sievgene

myPresto 5.0

114.4. in-silico Screening
myPresto performs docking calculations of combinations of proteins and low-molecular compounds,
and stores the data. Considering the number of combinations that are possible using 181 types ofproteins and 2 million low molecules, docking must be performed more than 181 x 2 million = 360
million times. For this reason, we improved work efficiency by automating the majority of the data
storage tasks. We also automated the screening process to allow users to perform screening using
any desired protein and low molecule. Available screening methods are MTS (Multiple Target
Screening) and DSI (Docking Score Index).
•MTS: For a target protein, this method examines the order of docking scores of low-molecularcompounds and selects compounds that rank high with that target protein.
•DSI: For each low-molecular compound, this method examines the patterns of the protein docking
scores and selects low molecules whose patterns resemble the docking score pattern of the specified
low-molecular compound.
MTS method with machine-learning, ML-MTS, is also prepared for high accuracy. For these
program are used depending whether the 3D structure of the target protein receptor is known or not,and whether the known ligands exist or not.
myPresto system provides the following programs and data for in-silico screening from 2
million small chemical compounds.
(1) Scripts for screening calculations(2) 3D database for 2 million chemical compounds, LigandBOX(3) Interaction matrix for the above (2) database
Scripts at the above (1) make it possible to perform effective screening from 2 million chemicalcompounds, using many possible CPU cores. For example, when 200 CPU cores are available,
complete parallel computation using 200 CPU cores can be done, where each core computes
screening from 10,000 chemical compounds. Some parts of the scripts use Job scheduling program,which is LSF in the default scripts. Users should change these parts, using bsub or qsub commands.
LigandBOX mentioned at the above (2) is an open database, containing the three-dimensional(3D) molecular structures and atomic charges of chemical compounds, which are available fromindustries. Some are collected from the KEGG DRUG database. A package including 2 million
chemical compounds in mol2 format is also provided.
The interaction matrix at the above (3) is necessary for DSI, MTS and ML-MTS methods. Here,docking scores for 181 referenced protein vs 2 million chemical compounds are included. (181 x
2,000,000).
The

packages,sievgene_packYYMMDD.tar.gz,

screening_packYYMMDD.tar.gz,

andscreening_dataYYMMDD.tar.gz are available for in-silico screening.

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myPresto also provides tools for ensemble docking, where docking simulations are made for a lot ofstructures generated by MD trajectories. When a few putative template receptor structures are
selected, universal active probes (UAPs) are used. A program package for the ensemble docking isavailable as UAPyymmdd.tar.gz

Fig. 3. Example of ensemble docking. First, MD simulation of a receptor protein in water isperformed (Upper left). Then, about 100 template receptor structures are randomly selected (Upperright). By using UAPs, about 5 templates are selected (Lower right). Finally, best ligand candidates
are given by docking calculations (Lower left).

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4.5. Search Similar Chemical Compounds : TGS(1) Substrucure_search
A ligand-based drug screening program based on chemical compound structure comparison. A
substructure search method based on the molecular structure by using the Ullman’s method.
A package program is available as substructure_searchYYMMDD.tar.gz(2) TGS: Topological Graph Search (A Similarity Search Using Molecular Topological Graphs)
A similarity search method based on eigen values of molecular edge matrix. ( Y. Fukunishi, H.
Nakamura. “A similarity search using molecular topological graphs”, Journal of Biomedicine andBiotechnology, Volume 2009 (2009), Article ID 231780)
A package program is available as TGSyymmdd.tar.gz

4.6. Precise Docking: sievgene_NMR and sievgene_MVO(1) sievgene_NMR: SIEVinG ENginE for NMR
A protein-compound docking program for prediction of protein-ligand complex structure withusing NMR signal of ligand. The prediction accuracy is improved approximately twice comparing tothe original sievgene by using the DIRECTION NMR signal of ligand. (Fukunishi, Y., Mizukoshi,Y., Takeuchi, K., Shimada, I., Takahashi, H., Nakamura, H. (2012) J. Mol. Graph. Model. 31, 20-27)
Last update on May 11,2012(2) sievgene_MVO: SIEVinG ENginE for Maximum Volume Overlap
A protein-compound docking program for prediction of protein-ligand complex structure / drug
screening with using a given known-ligand docking pose. This software performs a ligand docking
and overlapping the ligand onto the given known-ligand structure given by the user at the same time.
It is a combination of docking and similarity search. (Fukunishi, Y., Nakamura, H. (2012)
Pharmaceuticals 5, 1332-1345)

4.7. Estimate of Binding Free Energy: sievgene_DIAV
sievgene_DIAV, SIEVinG ENginE with DIAV method, is a protein-compound docking
program, sievgene, with DIAV method to estimate protein-compound binding free energy morecorrectly than the original sievgene does (less than about 1.3 kcal/mol). (Fukunishi, Y., Nakamura, H.
(2013) Pharmaceuticals 6, 604-622). This uses short MD simulation for an apo-receptor protein.
A program package is available as sievgene_DIAVyymmdd.tat.gz

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4.8. Estimate of Precise Binding Free Energy: SRPGSRPG (Smooth Reaction Path Generation) method is available to estimate very precise binding freeenergy, ΔG, of ligand, by first preparing a smoothed path, on which a ligand leaves the target
receptor protein. The path was first computed by a filling potential method (), which was thensmoothed by approximated with a Legendre polynomial. The PMF (Potential of Mean Force) at eachpoint on the smoothed path was computed by umbrella sampling method. (Fukunishi, Y., Mikami,Y., Nakamura, H. (2003) J. Phys. Chem. B. 107, 13201-13210; Fukunishi, Y., Mashimo, T., Orita,
M., Ohno, K., Nakamura, H. (2009) J. Chem. Inform. Model. 49, 925-933; Nguyen, H., Tran, T.,
Fukunishi, Y., Higo, J., Nakamura, H., Le, L. (2015) J. Chem. Inform. Model. 55, 1936-1943)
This program is included in a cosgene package (cosgene_packYYMMDD.tar.gz) and a cosgene
samplepackage(cosgene_sample_packYYMMDD.tar.gz).

Samplefiles

areincludedin

SPRG_sampleYYMMDD.tar.gz.

4.9. Prediction of Solubility and Aggregator: LogS_predictor
A solubility (LogS) predictor based on molecular descriptor and salvation free energy calculation.
Aggregators (frequent hitters) can be predicted based on the calculated LogS values (Mashimo, T.,
Fukunishi, Y., Orita, M., Katayama, N., Fujita, S., Nakamura, H. (2010) International Journal ofHigh Throughput Screening, 1, 99-107)
A program package is available as LogS_predictiorYYMMDD.tar.gz

4.10. Search pockets from a protein surface: MolSite
MolSite predicts ligand-binding site of target protein and its affinity by a compound docking
simulation (Fukunishi, Y., Nakamura, H. (2011) Protein Science 20, 95-106.)
A program package is available as MolSiteYYMMDD.tar.gz

4.11. 3D structure construction from 2D information of Chemical Compounds:
3DdataConstruction
A tool box for 3D mol2 file generation from 2D mol2 file. It can generate 3D compound databasefrom a 2D chemical compound catalog.
A program package is available as 3DdataConstructionYYMMDD.tar.gz

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4.12. Editing Tool of Chemical Compounds: EditMol
A part of a chemical compounds in mol2 format can be edited by a tool, EditMol.
A program package is available as EditMol_YYMMDD.tar.gz.

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5. Tool Programs
There are many tool programs included in myPresto as shown below. They are available astoolsYYMMDD.tar.gz, or included in the relating program packages.
The details of these tools are described in tools_manual_v5.000_en_YYMMDD.tar.gz•

set_water•

mergetpl•

SHAKEinp•

RIGIDinp•

GBSAinp•

reweightFB•

reweightST•

reweightGST•

selection•clustering•

Gamess2tplinp•

Gauss2tplinp•

tpl2mol2•

add_ion•confgene•confgeneC

•

FEP

•

Hgene

•

MVO

•

trans_code•

tpl2capbc

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6. Configuration of Environment Variables
The directories are designed so that users can work under the directories, which are generated byuncompressing the downloaded compressed files of myPresto version 5.0. Therefore, in many cases,
the environment variables such as paths are not particularly set, but only some relative paths are
assigned at executing the program.
When a path to the myPresto program is included as PATH, users are not required to make any
configurations by inputting the path information.
Followings are the example cases for execution of myPresto programs.
In the case, where the path information is not assigned:% ../bin/sievgene < control
Here, “../bin/” is the relative path for sievgene program.
In the case, where the path information is assigned:% sievgene < control

The followings indicate the environment variables and how to assign the path information.
• Environment Variables used in myPresto
Environment variable:

meaning of the variable

PATH

:

TPL_INPUT_PATH： input file directory for tplgeneX

TPL_OUTPUT_PATH： output file directory for tplgeneX

TPL_DB_PATH： force-field libraries directory for tplgeneX

TPLL_INPUT_PATH： input file directory for tplgeneL

TPLL_OUTPUT_PATH： output file directory for tplgeneL

TPLL_DB_PATH： force-field libraries directory for tplgeneL

Path to the program

In particular, TPL_DB_PATH and TPLL_DB_PATH are important for the usage of tplgeneX andtplgeneL.

myPresto 5.0

18[Example]
In

the

case

when

the

force-fieldparametersfor

tplgeneL

is

set

at

“/home/user01/myPresto/tplgeneL/DB”:
Configuration of the environment variables depends on shell (the underlines are user’s inputs):(1) In case of bash:% export TPLL_DB_PATH=/home/user01/myPresto/tplgeneL/DB(2) In case of csh:
% setenv TPLL_DB_PATH /home/user01/myPresto/tplgeneL/DB

When the paths to the directories configured by the environment variables are fixed, it is useful todescribe them in the LOGIN scripts like “.bashrc”or “.cshrc”.
The current shell is confirmed by the command below.
% ps

For the programs, tplgeneX and tplgeneL, bin/exec_tplgeneX.sh and bin/exec_tplgeneL.sh areprepared in cosgene_pack and sievgene_pack, respectively. These shells configure TPL_DB_PAH
and TPLL_DB_PATH, respectively, and so tplgeneX and tplgeneL can run without any
configurations by users themselves.

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7. List of Files to be Disseminated
The myPresto version 5.0 files disseminated are as follows:

tplgeneXYYMMDD.tar.gz
tplgeneLYYMMDD.tar.gz
pdbcheckYYMMDD.tar.gz
HgeneYYMMDD.tar.gz
sievgene_packYYMMDD.tar.gz
MolSiteYYMMDD.tar.gz
sceeening_packYYMMDD.tar.gz
UAPYYMMDD.tar.gz
screening_dataYYMMDD.tar.gz (Only this file is disseminated from Next Generation Natural
Product Chemistry (N2PC), not from Web site. Please contact N2PC.)
cosgene_packYYMMDD.tar.gz
cosgene_sample_packYYMMDD.tar.gz
SRPG_sampleYYMMDD.tar.gz
psygene-GYYMMDD.tar.gz
3DdataConstructionYYMMDD.tar.gz
EditMol_YYMMDD.tar.gz
LogS_predictorYYMMDD.tar.gz
TGSYYMMDD.tar.gz
substructure_searchYYMMDD.tar.gz
SyntheticAccessibilityYYMMDD.tar.gz
sievgene_DIAVYYMMDD.tar.gz
sievgene_MVOYYMMDD.tar.gz
sievgene_NMRYYMMDD.tar.gz
MD-MVOYYMMDD.tar.gz
toolsYYMMDD.tar.gz
LibMyPrestoYYMMDD.tar.gz
doc_enYYMMDD.tar.gz

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8. List of Documents
Documents in myPresto version 5.0 are as follows. They are included in doc_enYYMMDD.tar.gz orin the directory of the relating program, “doc/”.
user_manual_v5.000_en_YYMMDD.pdf(YYMMDD shows Year/Month/Date)tplgeneX_manual_v5.000_en_YYMMDD.pdf
tplgeneL_manual_v5.000_en_YYMMDD.pdf
Hgene_manual_v5.000_en_YYMMDD.pdf
sievgene_manual_v5.000_en_YYMMDD.pdf
cosgene_manual_v5.000_en_YYMMDD.pdf
cosgene_sample_manual_ v5.000_en_YYMMDD.pdf
psygene-G_manual_v5.000_en_YYMMDD.pdf
tools_manual_v5.000_en_YYMMDD.pdf
VCOL_manual_v5.000_en_YYMMDD.pdf

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9. References
Please refer the following References when you make any presentation for myPresto.
Entire myPresto system and Filling potential/SRPG method
1) "The filling potential method: A method for estimating the free energy surface for protein-ligand
docking", Yoshifumi Fukunishi, Yoshiaki Mikami, and Haruki Nakamura, J. Phys. Chem. B.
(2003) 107, 13201-13210.
2) “Protein-ligand binding free energy calculation by the smooth reaction path generation (SRPG)
method”, Yoshifumi Fukunishi, Daisuke Mitomo, and Haruki Nakamura, J. Chem. Inf. Model.,(2009) 49, 1944-1951.
3) “Computational Study of Drug Binding Affinity to Influenza A Neuraminidase Using Smooth
Reaction Path Generation (SRPG) Method”, Nguyen, H., Tran, T., Fukunishi, Y., Higo, J.,
Nakamura, H., Le, L. Journal of Chemical Information and Modeling, (2015) 55, 1936-1943.
cosgene with Multicanonical MD
4) "Determination of multicanonical weight based on a stochastic model of sampling dynamics", Jae
Gill Kim, Yoshifumi Fukunishi, Akinori Kidera and Haruki Nakamura, Physical Review E (2003)
68, 021110.
5) "Multicanonical molecular dynamics algorithm employing adaptive force-biased iteration
scheme", Jae Gil Kim, Yoshifumi Fukunishi, Haruki Nakamura, Phys. Rev. E (2004) 70, 057103.
Particle Mesh Ewald (PME)
6) “A smooth particle meth Ewald method” U.Essmann, L.Perera, M.L.Berkowitz, T.Darden, H.Lee
and L.G.Pedersen. (1995) J. Chem. Phys. 103, 8577-8593.
Accessible surface area (ASA)
7) “Physicochemical evaluation of protein folds predicted by threading” Kinjo, A. R., Kidera, A.,
Nakamura, H., Nishikawa, K. (2001) Eur Biophys J 30, 1-10.
Fast Multipole Method (FMM)
8) “Scalable variants of multipole-accelerated algorithms for molecular dynamics applications”In
Proceedings of the Seventh SIAM Conference on Parallel Processing for Scientific Computing,February 1995, J. A. Board, Z. S. Hakura, W. D. Elliott, W. T. Rankin.
9) W. T. Rankin,“Efficient Parallel Implementations of Multipole Based N-Body Algorithms.“PhDthesis, Duke University, Department of Electrical and Computer Engineering, P.O.Box 90291,
Durham, NC 27708-0291, April 1999.
10) W. T. Rankin, DPMTA –Distributed Parallel Multipole Tree Algorithm, Duke University,

myPresto 5.022Durham, NC (2002).
psygene/psygene-G11) "Molecular Dynamics Simulations Accelerated by GPU for Biological Macromolecules with a
Non-Ewald Scheme for Electrostatic Interactions", Tadaaki Mashimo, Yoshifumi Fukunishi,
Narutoshi Kamiya, Yu Takano, Ikuo Fukuda, Haruki Nakamura, J. Chem. Theory Comput. (2013)
9, 5599-5609.
sievgene12) "Similarity among receptor pockets and among compounds: Analysis and application to in silico
ligand screening", Y. Fukunishi, Y. Mikami, and H. Nakamura, The Journal of Molecular
Graphics and Modelling 24 (2005) 34-45.
Sievgene_NMR
13) Yoshifumi Fukunishi, Yumiko Mizukoshi, Koh Takeuchi, Ichio Shimada, Hideo Takahashi,
Haruki Nakamura. Protein-ligand docking guided by ligand pharmacophore-mapping
experiment by NMR. Journal of Molecular Graphics and Modelling, 2011, 31, 20-27.
Multiple Target Screening (MTS)
14) "Multiple target screening method for robust and accurate in silico screening", Y. Fukunishi, Y.
Mikami, S. Kubota, H. Nakamura, Journal of Molecular Graphics and Modelling,25, 61-70(2005).
15) "Noise reduction method for molecular interaction energy: application to in silico drug screening
and in silico target protein screening", Y. Fukunishi, S. Kubota, H. Nakamura, Journal ofChemical Information and Modeling, 46, 2071-2084 (2006).
16) "Improvement of protein-compound docking scores by using amino-acid sequence similarities ofproteins", Y. Fukunishi, H. Nakamura, Journal of chemical information and modeling, 48,
148-156 (2008)
Docking Score Index (DSI)17) "Classification of chemical compounds by protein-compound docking for use in designing a
focused library", Y. Fukunishi, Y. Mikami, K. Takedomi, M. Yamanouchi, H. Shima, H.
Nakamura, Journal of Medicinal Chemistry, 49, 523-533 (2006).
18) "An efficient in silico screening method based on the protein-compound affinity matrix and its
application to the design of a focused library for cytochrome P450 (CYP) ligands", Y. Fukunishi,
S. Hojo, H.Nakamura, Journal of chemical information and modeling, 46, 2610-22 (2006).

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Maximum Volume Overlap (MVO)
19) "Prediction of protein-ligand complex by docking software guided by other complex structures",Y. Fukunishi, H. Nakamura, Journal of Molecular Graphics and Modelling, 26 (2008) 1030-1033.
Molecular-dynamics Maximum Volume Overlap (MD-MVO)20) "Anew

methodforin-silico

drug

screeningandsimilarity

searchusing

molecular-dynamics maximum-volume overlap (MD-MVO) method", Y. Fukunishi, H.
Nakamura, Journal of Molecular Graphics and Modelling, 2009, 27, 628-636.
TGS21) "A similarity search using molecular topological graphs", Y. Fukunishi, H. Nakamura,Journal of
Biomedicine and Biotechnology, Volume 2009 (2009), Article ID 231780
LigandBOX22) "Advanced in-silico drug screeing to achieve high hit ratio-development of 3D-compound
database", Yoshifumi Fukunishi, Yuusuke Sugihara, Yoshiaki Mikami, Kohta Sakai, Hiroshi
Kusudo, Haruki Nakamura,

Synthesiology, 2009, 2, 60-68.

23) "LigandBox: A database for 3D structures of chemical Compounds", Takeshi Kawabata, Yusuke
Sugihara, Yoshifumi Fukunishi, Haruki Nakamura, Biophysics (2013) 9, 113-121.
Sptool for solubility (LogS) and aggregator (frequent hitter) prediction24) Tadaaki Mashimo, Yoshifumi Fukunishi, Masaya Orita, Naoko Katayama, Shigeo Fujita, Haruki
Nakamura, Quantitative analysis of aggregation-solubility relationship by in-silico solubility
prediction, International Journal of High Throughput Screening, 2010:1, 99-107.
Prediction of ligand-binding site, MolSite
25) Yoshifumi Fukunishi, Haruki Nakamura. “Prediction of ligand-binding sites of proteins bymolecular docking calculation for a random ligand library”, Protein Science. 2011: 20, 95-106.
Universal active probe (UAP)26)

Fukunishi, Yoshifumi; Ono, Kazuki; Orita, Masaya; Nakamura, Haruki, Selection of in-silico
drug screening result by using universal active probes (UAPs), Journal of Chemical
Information and Modeling, 2010, 50, 1233-1240.

27)

Mitsuhito Wada, Eiji Kanamori, Haruki Nakamura, Yoshifumi Fukunishi, Selection of
in-silico drug screening results for G-protein-coupled receptors by using universal active probe.

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Journal of Chemical Information and Modeling. 2011, 51 (9) 2398-2407.
BindMol28) Yoshifumi Fukunishi. Prediction of positions of active compounds makes it possible to increase
activity in fragment-based drug development. Pharmaceuticals. 2011, 4, 758-769.
Sievgene-MVO
29) Yoshifumi Fukunishi, Haruki Nakamura. “Integration of Ligand-Based Drug Screening with
Structure-Based Drug Screening by Combining Maximum Volume Overlapping Score with Ligand
Docking”, Pharmaceuticals. 2012: 5, 1332-1345.

myPresto 5.000

myPresto 5.0