An Automated force field Topology Builder. (ATB) and repository: version 1.0

Size: px

Start display at page:

Download "An Automated force field Topology Builder. (ATB) and repository: version 1.0"

Warren Matthews
5 years ago
Views:

1 Supporting information An Automated force field Topology Builder (ATB) and repository: version 1.0 Alpeshkumar K. Malde, 1 Le Zuo, 1 Matthew Breeze, 1 Martin Stroet, 1 David Poger, 1 Pramod C. Nair, 1 Chris Oostenbrink 2,3 and Alan E. Mark *,1,4 1 School of Chemistry and Molecular Biosciences, 2 Leiden/Amsterdam Center for Drug Research, Division of Molecular Toxicology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands, 3 Institute of Molecular Modeling and Simulation, University of Natural Resources and Applied Life Sciences, Vienna, Austria, and 4 Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia. * Corresponding author AUTHOR ADDRESSES: a.e.mark@uq.edu.au, a.malde@uq.edu.au 1

2 Table S1. A comparison between the experimental and calculated free energies of hydration ( G hyd ) for biologically relevant small organic molecules using parameters assigned by the Automated Topology Builder (ATB). The RMSD between the QM optimized structure as obtained from the ATB and the one obtained after MD simulation of 1 ns in SPC water using the GROMOS force field assigned by the ATB is also shown. Values are in kj.mol -1. No errors have been reported for the experimental data on these molecules. RNME on the ATB Name G hyd; exp G hyd; cal G hyd;cal G hyd; exp Alcohols ISOP Isopropanol ± G090 2-methyl-1-propanol ± G091 2-butanol ± G092 2-methyl-2-propanol ± G094 3-methyl-1-butanol ± G095 2-pentanol ± G096 3-pentanol ± G097 2-methyl-2-butanol ± G099 2,3-dimethyl-2-butanol ± G100 3-hexanol ± G101 4-methyl-2-pentanol ± G102 2-methyl-3-pentanol ± G103 2-methyl-2-pentanol ± G105 4-heptanol ± G108 Cyclopentanol ± G109 Cyclohexanol ± G110 Cycloheptanol ± G111 Phenol ± F035 2-methylphenol ± _I0H 4-methylphenol ± Average 2.4 Aldehydes G146 Ethanal ± G147 Propanal ± G148 Butanal ± G149 Pentanal ± G158 Benzaldehyde ± Average 2.0 Alkanes _ICJ Ethane ± _I0I Propane ± G006 Pentane ± G034 Methyl butane ± G008 Dimethyl propane ± _ICZ Hexane ± G013 Heptane ± G015 Octane ± Average 0.4 Alkenes G026 Ethene ± G027 Propene ± G028 1-Butene ± G031 trans-2-pentene ± G007 1-hexene ± G039 Cyclopentene ± G040 Cyclohexene ± Average 3.9 Alkyl benzenes G058 Benzene ± All-atom RMSD (nm) 2

3 _I0L Methyl benzene (toluene) ± G060 Ethyl benzene ± G064 Propyl benzene ± G067 n-butyl benzene ± G065 Isopropyl benzene ± G068 sec-butyl benzene ± Average 3.0 Alkynes G049 Ethine ± G050 Propine ± G051 1-Butine ± G052 1-Pentine ± G053 1-Hexine ± Average 5.0 Amides _I0X Acetamide ± _I0J Propyl amide ± G235 N-methyl acetamide ± G236 N,N-dimethyl acetamide ± Average 3.7 Amines (Primary) G191 Methyl amine ± G192 Ethyl amine ± G193 Propyl amine ± _I0F Butyl amine ± Average 8.5 Carboxylic acids _I0M Acetic acid ± _I0K Propanoic acid ± G161 Butanoic acid ± Average 3.5 Cycloalkanes G018 Cyclopropane ± G019 Cyclopentane ± G021 Methyl cyclopentane ± CHE Cyclohexane ± G022 Cycloheptane ± G023 Methyl cyclohexane ± Average 2.5 Esters G162 Methyl methanoate ± G163 Ethyl methanoate ± G164 Methyl ethanoate ± G165 Propyl methanoate ± G167 Ethyl ethanoate ± G168 Methyl propanoate ± G190 Methyl benzoate ± Average 5.1 Ketones G130 Dimethylketone ± G131 Methyl ethyl ketone ± G132 Methyl-1-propyl ketone ± G133 Diethyl ketone ± Average 2.1 Thiols and sulfides _I0A Methyl thiol ± G288 Ethyl thiol ± G289 Benzene thiol ± G290 Dimethyl sulfide ±

4 G291 Diethyl sulfide ± G292 Methyl thiobenzene ± Average 5.0 Overall average 3.3 4

5 Table S2. A comparison between the experimental and calculated free energies of hydration ( G hyd ) for the drug-like and drug molecules from SAMPL0, 1 and 2 challenges using parameters assigned by the Automated Topology Builder (ATB). The RMSD between the QM optimized structure as obtained from the ATB and the one obtained after MD simulation of 1 ns in SPC water using the GROMOS force field assigned by the ATB is also shown. Only molecules with 40 atoms are considered. Values are in kj.mol -1. RNME on the ATB Name Chemical structure G hyd; exp G hyd; cal G hyd;cal G hyd; exp ± error All-atom RMSD (nm) SAMPL0/CUP8 dataset M494 Glycerol triacetate -36.7± ± ± S002 Benzyl bromide -9.9± ± ± S003 Benzyl chloride -8.1± ± ± S004 m-bis-trifluoromethylbenzene 4.5± ± ± S005 N,N-dimethyl-p-methoxy benzamide -46.0± ± ± S006 N,N,4-trimethylbenzamide -40.8± ± ± S007 Bis-2-chloroethyl ether -17.7± ± ±

6 S008 1,1-diacetoxyethane -20.8± ± ± G253 1,1-diethoxyethane -13.7± ± ± G256 1,4-dioxane -21.1± ± ± M291 Diethyl propanedioate -25.1± ± ± G251 Dimethoxymethane -12.2± ± ± S013 Ethylene glycol diacetate -26.5± ± ± G254 1,2-diethoxyethane -14.8± ± ± G291 Diethyl sulfide -6.0± ± ± S016 Phenyl formate -16.0± ± ± F135 Imidazole -41.0± ± ± SAMPL1 dataset _JCE Nitroglycol -24.0± ± ± ,2-dinitroxypropane -20.7± ± ±

7 8003 Butyl nitrate -8.7± ± ± butyl nitrate -7.6± ± ± Isobutyl nitrate -7.9± ± ± Ethyleneglycol mononitrate -34.2± ± ± Alachlor -34.4± ± ± Aldicarb -41.2± ± ± Ametryn -32.0± ± ± Azinphosmethyl -42.0± ± ± Benefin -14.7± ± ±

8 8013 Bromacil -40.7± ± ± Captan -37.7± ± ± Carbaryl -39.5± ± ± Carbofuran -40.2± ± ± Carbophenothion -27.2± ± ± Chlordane -14.4± ± ±

9 8019 Chlorfenvinphos -29.6± ± ± Chloropicrin -6.1± ± ± Chlorpyrifos -21.1± ± ± Dialifor -24.0± ± ± Diazinon -27.1± ± ± Dicamba -41.3± ± ±

10 8026 Dichlobenil -19.7± ± ± Dinitramine -23.7± ± ± Dinoseb -26.1± ± ± Endosulfan alpha -17.7± ± ± Endrin -20.2± ± ± Fenuron -38.2± ± ±

11 8033 Heptachlor -10.7± ± ± Isophorone -21.7± ± ± Lindane -22.8± ± ± Malathion -34.1± ± ± Methomyl -44.6± ± ± Methyparathion -30.1± ± ± Nitroxyacetone -25.1± ± ±

12 8042 Oxamyl -42.6± ± ± Parathion -28.2± ± ± Pebulate -15.2± ± ± Phorate -18.3± ± ± Profluralin -10.3± ± ± Prometryn -35.3± ± ±

13 8048 Propanil -32.6± ± ± Pyrazon -68.7± ± ± Simazine -42.8± ± ± Terbacil -46.6± ± ± Terbutryn -27.9± ± ± Thifensulfurone -67.9± ± ± Trichlorofon -53.3± ± ±

14 8056 Trifluralin -13.6± ± ± Vernolate -17.3± ± ± amino-4 -nitroazobenzene -47.0± ± ± amino-4-anilinoanthraquinone -31.1± ± ± ,4,5,8-tetraminoanthraquinone -37.4± ± ± amino-anthraquinone -33.3± ± ±

15 8063 Pirimor (pirimacarb) -39.4± ± ± SAMPL2 dataset 2S01 Uracil -69.4± ± ± F008 5-bromouracil -76.0± ± ± S03 5-chlorouracil -74.2± ± ± S04 5-fluorouracil -70.8± ± ± S06 5-trilfuoromethyluracil -64.7± ± ± S07 6-chlorouracil -66.2± ± ± S08 Cyanuric acid - keto tautomer -76.4± ± ±

16 - Enol tautomer -75.0± S09 Caffeine -52.9± ± ± S11 Ethyl paraben -38.5± ± ± S12 Propyl paraben -39.2± ± ± S13 Butyl paraben -36.5± ± ± S14 Acetylsalicylic acid -41.6± ± ± S15 Diflunisal -39.3± ± ±

17 2S16 Flurbiprofen -35.2± ± ± S17 Ibuprofen -29.3± ± ± S18 Naproxen -42.7± ± ± S19 Phthalimide -40.2± ± ± S22 Sulfolane -36.0± ± ± S23 Ketoprofen -45.1± ± ± S24 Hexachlorobenzene -9.6± ± ± S25 Hexachloroethane -5.9± ± ±

18 2S26 Octofluorocyclobutane -12.6± ± ± S27 Trimethyl orthotrifluoroacetate -3.3± ± ± S28 Trimethyl phosphate -36.4± ± ± S29 4-nitroaniline -41.9± ± ± G250 Glycerol -56.1± ± ± S31 pentachloronitrobenzene -21.8± ± ±

Organic Chemistry. A. Introduction

Organic Chemistry. A. Introduction Organic Chemistry A. Introduction 1. Organic chemistry is defined as the chemistry of CARBON compounds. There are a huge number of organic compounds. This results from the fact that carbon forms chains