Chapter 4 Conclusions
4.2 Future works
Our scoring matrices consider considering the contact information of the steric and specific energies, but still not perfect. Several works might be able to improve our method to be better:
1. The weights of each term in our proposed scoring method will be obtained a good parameter sets by machine learning approach like genetic algorithm (GA), neural network (NN), or support vector machines (SVM).
2. For detecting possible transcription factor binding sites, more transcription factors which have crystal structures of protein-DNA complexes will be used to as the template. The high-score region predicted by our scoring method in promoter regions will be further verified.
3. Consider the occurrences number of interaction pairs, since that multiple hydrogen bonds has been observed appear in several cases. We roughly test this consideration in to ProNIT free energy data set, the performance is improve from -0.498 to -0.525.
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Table 1. List of the representative protein-DNA complex structure set. Each entry is provided with the four-digit PDB code, the protein chain identifier, the chain identifiers of dsDNA to which the protein is bound, the contact number , and the description of the protein.
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1a0a A CD 27 PHOSPHATE SYSTEM POSITIVE REGULATORY 1ais B CE 19 TRANSCRIPTION INITIATION FACTOR IIB 1am9 A EFGH 36 STEROL REGULATORY ELEMENT BINDING PR
1an4 A CD 32 UPSTREAM STIMULATORY FACTOR 1apl C AB 45 MAT-ALPHA2 HOMEODOMAIN
1azp A BC 38 HYPERTHERMOPHILE CHROMOSOMAL PROTEIN 1b3t A CD 70 NUCLEAR PROTEIN EBNA1
1bdh A B 20 PURINE REPRESSOR
1bdt B EF 27 GENE-REGULATING PROTEIN ARC
1bf5 A BC 42 SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPT 1brn L A 25 BARNASE (E.C.3.1.27.-)
1bvo A D 16 TRANSCRIPTION FACTOR GAMBIF1
1c7y A BCDEFGHI 104 HOLLIDAY JUNCTION DNA HELICASE RUVA 1c9b M CDGHKLOP 38 GENERAL TRANSCRIPTION FACTOR IIB 1cdw A BC 74 TATA BINDING TBP
1cf7 A CD 35 TRANSCRIPTION FACTOR E2F-4 1cf7 B CD 22 TRANSCRIPTION FACTOR DP-2 1cgp A CDEF 42 CATABOLITE GENE ACTIVATOR C
1dc1 A WC 68 BSOBI RESTRICTION ENDONUCLEASE
1de9 B UVW 47 MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASE 1dfm A CD 76 ENDONUCLEASE BGLII
1dh3 A BD 21 TRANSCRIPTION FACTOR CREB
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1emh A BC 23 URACIL-DNA GLYCOSYLASE 1eoo A CD 66 TYPE II RESTRICTION ENZYME ECORV 1eyg C Q 82 SINGLE-STRAND DNA-BINDING PROTEIN 1f0v B N 11 RIBONUCLEASE A
1f2i H AB 42 FUSION OF N-TERMINAL 17-MER PEPTIDE EXTENSION 1f4k B DE 43 REPLICATION TERMINATION PROTEIN
1f6o A DE 38 3-METHYL-ADENINE DNA GLYCOSYLASE 1fiu D GKHL 54 TYPE II RESTRICTION ENZYME NGOMI 1fok A BC 107 FOKI RESTRICTION ENDONUCLEAS 1fos F AB 22 C-JUN PROTO-ONCOGENE PROTEIN
1fzp B WK 8 STAPHYLOCOCCAL ACCESSORY REGULATOR A 1gd2 E AB 33 TRANSCRIPTION FACTOR PAP1
1gm5 A XYZ 46 RECG
1gt0 D AB 61 TRANSCRIPTION FACTOR SOX-2
1gxp F GH 47 PHOSPHATE REGULON TRANSCRIPTIONAL REGULATORY 1h88 B DE 29 CCAAT/ENHANCER BINDING PROTEIN BETA
1h88 C DE 50 MYB PROTO-ONCOGENE PROTEIN 1h9d A EF 35 CORE-BINDING FACTOR ALPHA SUBUNIT1
1h9t A XY 50 FATTY ACID METABOLISM REGULATOR PROTEIN 1hbx G CW 46 ETS-DOMAIN PROTEIN ELK-4
1hdd C AB 38 ENGRAILED HOMEODOMAIN
1hf0 A MN 69 OCTAMER-BINDING TRANSCRIPTION FACTOR 1
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1ign A CD 124 RAP1
1iu3 F ABDE 42 SeqA protein
1ixy A CE 37 DNA beta-glucosyltransferase
1j1v A BC 50 Chromosomal replication initiator protein dna 1jb7 A D 60 telomere-binding protein alpha subunit
1jt0 A EF 37 HYPOTHETICAL TRANSCRIPTIONAL REGULATOR IN QAC 1k3w A BC 34 Endonuclease VIII
1k78 I CDGH 41 Paired Box Protein Pax5
1k82 A FJ 8 formamidopyrimidine-DNA glycosylase 1keg H A 8 Anti-(6-4) photoproduct antibody 64M-2 Fab 1m07 A CD 24 Ribonuclease
1m18 H IJ 28 Histone H2B.1
1m3q A BC 46 8-oxoguanine DNA glycosylase 1m6x B EIFJGH 92 Flp recombinase
1mdm A CD 97 PAIRED BOX PROTEIN PAX-5
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1mje A C 40 breast cancer 2
1mjq H KL 25 METHIONINE REPRESSOR 1mm8 A BC 76 Tn5 Transposase
1n6j B CD 31 Myocyte-specific enhancer factor 2B 1nkp B FG 28 Max protein
1nlw A FG 25 MAD PROTEIN
1noy B S 20 DNA POLYMERASE (E.C.2.7.7.7)
1odh A CD 42 MGCM1
1oe6 B EF 11 SINGLE-STRAND SELECTIVE MONOFUNCTIONAL URACIL 1oh6 A EF 63 DNA MISMATCH REPAIR PROTEIN MUTS
1pgz A B 40 Heterogeneous nuclear ribonucleoprotein A1 1pp8 F EIYKTRJG 50 39 kDa initiator binding protein
1qpi A M 9 TETRACYCLINE REPRESSOR 1qrv A CD 42 HIGH MOBILITY GROUP PROTEIN D 1qum A BCD 54 ENDONUCLEASE IV
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1qzh D J 40 Protection of telomeres protein 1 1r0o A CD 35 Ultraspiracle protein
1r71 A EIFJ 70 Transcriptional repressor protein korB 1r8e A B 20 multidrug-efflux transporter regulator 1rb8 F X 5 Capsid protein
1rzr A EB 45 Glucose-resistance amylase regulator 1s9k D AB 26 Proto-oncogene protein c-fos
1sax B CD 34 Methicillin resistance regulatory protein mec 1seu A BCD 80 DNA topoisomerase I
1sfu A CD 16 34L protein
1skn P AB 37 DNA-BINDING DOMAIN OF SKN-1 1svc P D 29 NUCLEAR FACTOR KAPPA-B (NF-KB) 1t2k D EF 25 Cyclic-AMP-dependent transcription factor ATF 1t39 A CD 33 Methylated-DNA--protein-cysteine methyltransf 1t39 A EF 9 Methylated-DNA--protein-cysteine methyltransf 1tc3 C AB 51 TC3 TRANSPOSASE
1tez C M 15 Deoxyribodipyrimidine photolyase 1tez C N 11 Deoxyribodipyrimidine photolyase
1trr A CI 43 TRP REPRESSOR
1ttu A BC 52 lin-12 And Glp-1 transcriptional regulator 1tx3 C EFGH 79 Type II restriction enzyme HindII
1u1l A B 40 Heterogeneous nuclear ribonucleoprotein A1 1u3e M ABC 128 HNH homing endonuclease
1u78 A BC 99 transposable element tc3 transposase 1u8b A BC 35 Ada polyprotein
1u8r B EF 36 Iron-dependent repressor ideR 1v14 C IJ 34 COLICIN E9
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
1w0t A CD 47 TELOMERIC REPEAT BINDING FACTOR 1 1w36 B Y 47 EXODEOXYRIBONUCLEASE V BETA CHAIN 1w36 C Y 27 EXODEOXYRIBONUCLEASE V GAMMA CHAIN
1wte A XY 77 EcoO109IR
1x9n A BCD 123 DNA ligase I 1x9w A CD 78 DNA polymerase
1xbr B CD 46 T PROTEIN
1xc8 A BC 42 Formamidopyrimidine-DNA glycosylase 1xf2 L T 7 antibody light chain Fab
1xjv A B 50 Protection of telomeres 1 1xpx A DC 19 Protein prospero
1ya6 B CD 27 DNA alpha-glucosyltransferase 1yfi B EF 62 Type II restriction enzyme MspI
1z9c F KL 56 Organic hydroperoxide resistance transcriptio
1zaa C AB 67 ZIF268
1zg1 B CD 34 Nitrate/nitrite response regulator protein na 1zlk A CD 36 Dormancy Survival Regulator
1zme C AB 24 PROLINE UTILIZATION TRANSCRIPTION ACTIVATOR 1zqk A TP 34 DNA POLYMERASE BETA (E.C.2.7.7.7)
1zr4 B JIK 74 Transposon gamma-delta resolvase 1zrc A WXYZ 36 Catabolite gene activator
1zs4 A UT 32 Regulatory protein CII
1zzj B D 31 Heterogeneous nuclear ribonucleoprotein K 2a3v D GH 101 site-specific recombinase IntI4
2ac0 D GH 26 Cellular tumor antigen p53
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
2bnw A EFGH 21 ORF OMEGA
2bop A B 14 E2
2bqu A PT 72 DNA POLYMERASE IV 2bsq G IJ 18 TRAFFICKING PROTEIN A
2bzf A BC 29 BARRIER-TO-AUTOINTEGRATION FACTOR 2c5r F YZ 9 EARLY PROTEIN P16.7
2c62 A C 32 ACTIVATED RNA POLYMERASE II TRANSCRIPTIONAL C 2c9l Y AB 25 BZLF1 TRANS-ACTIVATOR PROTEIN
2ccz A C 18 PRIMOSOMAL REPLICATION PROTEIN N 2d5v A CD 71 Hepatocyte nuclear factor 6
2dem A CD 45 uracil-DNA glycosylase
2dgc A B 14 GCN4
2dpj A PT 48 DNA polymerase iota
2drp A BC 50 TRAMTRACK DNA-BINDING DOMAIN 2dwl C F 13 Primosomal protein N
2e1c A BD 26 Putative HTH-type transcriptional regulator P 2e52 C FH 86 Type II restriction enzyme HindIII
2h8c B WX 15 Crossover junction endodeoxyribonuclease rusA 2h8r B EF 58 Hepatocyte nuclear factor 1-beta
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
2hvr B CD 12 T4 RNA ligase 2
2hzv A IJ 22 Nickel-responsive regulator 2hzv H KL 30 Nickel-responsive regulator
2i06 A BC 135 DNA replication terminus site-binding protein 2i9k A CD 89 Modification methylase HhaI
2o61 A EF 149 Transcription factor p65/Interferon regulator 2o6m A CD 58 Intron-encoded endonuclease I-PpoI
2o8c A EF 13 DNA mismatch repair protein Msh2 2o8f B EF 59 DNA mismatch repair protein MSH6 2oa8 B C 29 Three prime repair exonuclease 1 2oaa A CDEF 116 R.MvaI
2ofi A CB 34 3-methyladenine DNA glycosylase I, constituti 2oh2 A SQ 74 DNA polymerase kappa
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
2pfj A ZY 43 Endodeoxyribonuclease 1 2pi0 D EF 54 Interferon regulatory factor 3
2q2k A F 15 Hypothetical protein 2q2u A EF 94 Chlorella virus DNA ligase
2qby B CD 63 Cell division control protein 6 homolog 3 2qfj A C 7 FBP-interacting repressor
2qhb A EF 37 Telomere binding protein TBP1 2ql2 A EF 23 Transcription factor E2-alpha 2ql2 B EF 20 Neurogenic differentiation factor 1 2qnf B EF 23 Recombination endonuclease VII 2qsg A WY 69 DNA repair protein RAD4 2v6e A CDEF 138 PROTELEMORASE 2ve9 D IJKL 30 DNA TRANSLOCASE FTSK
2w42 A PQ 48 PUTATIVE UNCHARACTERIZED PROTEIN 2w7n A EFGH 75 TRFB TRANSCRIPTIONAL REPRESSOR PROTEIN
2wb2 A CD 31 PHOTOLYASE
2yvh B GH 31 Transcriptional regulator
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
2z70 A B 27 Ribonuclease I
2z9o B CD 48 Replication initiation protein
2zhg A B 13 Redox-sensitive transcriptional activator sox 3b39 A C 17 DNA primase
3bam B CDE 50 RESTRICTION ENDONUCLEASE BAMHI 3bdn A CD 35 Lambda Repressor
3bep A CD 14 DNA polymerase III subunit beta 3bm3 A CD 68 PspGI restriction endonuclease
3bs1 A BC 35 Accessory gene regulator protein A
3btx A BC 54 Alpha-ketoglutarate-dependent dioxygenase alk 3c0x A BCD 113 Intron-encoded endonuclease I-SceI
3c25 A CD 87 NotI restriction endonuclease
3cvs C GH 22 DNA-3-methyladenine glycosylase 2 3d0p A B 16 Ribonuclease H
3d2w A B 24 TAR DNA-binding protein 43 3d70 A B 21 BMR promoter DNA
3dfv C YZ 55 Trans-acting T-cell-specific transcription fa 3dlh A X 108 Argonaute
3dnv B T 17 HTH-type transcriptional regulator hipB 3dsc A B 26 DNA double-strand break repair protein mre11 3dvo B EF 72 SgraIR restriction enzyme
3dzy D CF 49 Peroxisome proliferator-activated receptor ga 3e00 A CF 37 Retinoic acid receptor RXR-alpha
3e54 A CDEF 93 RRNA intron-encoded endonuclease 3e6c C BA 36 Cyclic nucleotide-binding protein 3eh8 A BC 125 Intron-encoded DNA endonuclease I-AniI
3ei1 B GH 27 DNA damage-binding protein 2 3eyi A CD 17 Z-DNA-binding protein 1
3f2c A PT 95 GEOBACILLUS KAUSTOPHILUS DNA POLC
PDB Code
Protein
Chain DNA Chains Contact
number Protein Description
3f8i B FG 40 E3 ubiquitin-protein ligase UHRF1 3fc3 A CD 58 Restriction endonuclease Hpy99I 3fhz A GHKL 40 Arginine repressor
3g73 A CD 35 Forkhead box protein M1
3hts B A 16 HEAT SHOCK TRANSCRIPTION FACTOR 3orc A RS 22 CRO REPRESSOR
Table 2. Thermodynamic data of single residue mutations. Each entry is provided with the four-digit PDB code, the protein chain identifier, the wild-type amino acid of protein, the position of amino acid, the mutated amino acid, and the free energy change ∆∆G, which was calculated as ∆G(mutate) - ∆G(wild).
PDB Code Protein
Chain Wild-type Position Mutate ∆∆G
1ais A E 12 A 0.00
PDB Code Protein
Chain Wild-type Position Mutate ∆∆G
1emh A R 276 C 0.58
PDB Code Protein
Chain Wild-type Position Mutate ∆∆G
1run A E 181 D 0.40 1tro A A 77 V 0.00 2bpf A R 283 A 0.84 2bpf A R 283 K 0.45 2bpg A Y 271 A 0.28 2bpg A Y 271 F 0.06 2bpg A Y 271 S 0.22 2hmi A W 153 A 0.30 2hmi A W 153 F -0.40 2hmi A W 153 Y 0.10
Figure 1. An example of residue–nucleotide interaction pair in 1zrc. A guanine base is making hydrogen bonds to an arginine amino acid. There are two contacts of hydrogen atoms on the arginine with oxygen or nitrogen atoms on the major groove edge of the guanine ring.
(A)
(B)
Figure 2. An example of constructing contact profile. (A) The 3-D structure of CRP protein binding with DNA. HTH motif of CRP chain A was colored in red; blue and green were each chain of double helix DNA. (B) The Contact profile of 1ZRC HTH motif. The contact pair is represented using the form “CP: NP R + CD: ND T”, where CP is the ID of the protein chain, NP
is the residue number, R is the residue symbol, CD is the ID of the DNA chain, ND is the nucleotide number, and T is the nucleotide symbol.
Figure 3. Frequency tables of eight interaction types. (Vss, Vsb, Vms, Vmb, Sss, Ssb, Sms, and Smb).
Figure 4. Log-odds score translated from frequency tables. (Vss, Vsb, Vms, Vmb, Sss, Ssb, Sms, and Smb).
Vss A C G T Vsb A C G T Vms A C G T Vmb A C G T
Gly ‐inf ‐inf ‐inf ‐inf Gly ‐inf ‐inf ‐inf ‐inf Gly 0.93 1.20 0.99 1.31 Gly 0.63 0.86 0.72 0.80
Ala ‐0.66 ‐0.72 ‐0.68 ‐0.28 Ala ‐0.37 ‐0.17 ‐0.17 ‐0.11 Ala 0.05 0.48 ‐0.03 1.24 Ala 0.26 0.30 0.35 0.60
Val ‐0.32 ‐0.46 ‐0.55 ‐0.38 Val ‐0.30 ‐0.18 0.04 ‐0.28 Val ‐0.64 ‐0.79 ‐0.30 ‐0.18 Val 0.02 0.18 0.36 0.10
Ile ‐0.40 ‐0.47 ‐0.66 ‐0.09 Ile ‐0.16 ‐0.06 ‐0.14 ‐0.24 Ile ‐0.48 ‐0.12 ‐0.37 0.26 Ile ‐0.01 0.20 0.22 ‐0.05
Leu ‐0.51 ‐0.61 ‐0.38 0.08 Leu ‐0.23 ‐0.09 0.05 ‐0.07 Leu ‐1.21 0.11 ‐0.42 ‐0.12 Leu ‐0.14 0.30 0.06 0.10
Pro ‐0.43 ‐1.28 ‐0.79 0.09 Pro ‐0.06 ‐0.30 ‐0.14 ‐0.11 Pro 0.36 ‐0.47 ‐1.34 0.72 Pro 0.02 0.06 0.17 0.27
Cys ‐0.77 0.04 ‐0.23 ‐0.16 Cys ‐0.33 ‐0.25 ‐0.36 ‐0.33 Cys 0.29 ‐0.81 ‐inf 0.20 Cys 0.17 0.26 0.55 ‐0.61
Met 0.26 ‐0.40 0.03 0.51 Met 0.07 ‐0.12 0.02 0.21 Met ‐0.08 ‐1.69 0.08 0.71 Met ‐0.45 ‐0.19 0.18 0.45
Phe ‐0.09 ‐0.35 0.02 0.34 Phe 0.13 0.02 0.09 0.24 Phe ‐0.13 ‐0.04 ‐0.38 0.12 Phe ‐0.30 ‐0.05 ‐0.23 ‐0.42
Tyr ‐0.10 0.29 0.06 0.52 Tyr 0.16 0.38 0.27 0.32 Tyr ‐0.44 ‐0.55 ‐0.98 ‐0.06 Tyr ‐0.55 ‐0.39 ‐0.80 ‐0.90
Trp ‐0.41 ‐0.06 ‐0.19 0.08 Trp ‐0.10 0.45 0.13 0.19 Trp ‐inf 0.08 ‐0.63 ‐0.41 Trp ‐1.65 ‐0.26 ‐0.49 ‐1.18
Ser ‐0.53 ‐0.56 ‐0.28 0.27 Ser ‐0.01 0.03 0.06 0.19 Ser ‐0.56 ‐0.06 0.30 0.63 Ser 0.19 0.29 0.35 0.35
Thr ‐0.48 ‐0.16 ‐0.34 0.13 Thr 0.02 0.07 0.16 0.25 Thr ‐0.07 ‐0.20 ‐0.79 0.33 Thr 0.02 0.03 0.27 0.18
Asn 0.32 0.16 0.22 0.33 Asn ‐0.04 ‐0.05 0.03 0.11 Asn ‐0.30 0.39 0.23 0.50 Asn ‐0.28 ‐0.20 ‐0.08 ‐0.11
Gln 0.30 0.25 0.29 0.32 Gln 0.08 ‐0.01 0.08 ‐0.05 Gln ‐0.59 ‐0.48 ‐0.61 ‐0.79 Gln ‐0.18 ‐0.28 ‐0.09 ‐0.25
Asp ‐0.66 0.56 ‐0.03 ‐0.51 Asp ‐0.31 ‐0.08 0.07 ‐0.57 Asp ‐0.05 0.12 ‐0.39 0.03 Asp ‐0.34 ‐0.28 0.17 ‐0.46
Glu ‐0.26 0.60 ‐0.21 0.16 Glu ‐0.43 ‐0.19 ‐0.10 ‐0.52 Glu ‐1.17 ‐0.07 ‐1.19 ‐0.16 Glu ‐0.45 ‐0.36 ‐0.03 ‐0.53
His ‐0.02 0.09 0.33 0.43 His 0.05 ‐0.11 0.05 0.34 His ‐1.09 0.16 ‐0.20 0.43 His ‐0.40 ‐0.51 ‐0.07 ‐0.18
Arg 0.42 0.55 0.79 0.58 Arg 0.18 0.21 0.22 0.34 Arg ‐0.76 ‐0.80 ‐0.78 ‐0.40 Arg ‐0.42 ‐0.49 ‐0.45 ‐0.37
Lys ‐0.26 ‐0.34 0.10 ‐0.33 Lys 0.18 0.27 0.08 0.13 Lys ‐1.25 ‐0.10 ‐0.62 ‐0.12 Lys ‐0.29 ‐0.05 ‐0.37 ‐0.29
Sss A C G T Ssb A C G T Sms A C G T Smb A C G T
Gly ‐inf ‐inf ‐inf ‐inf Gly ‐inf ‐inf ‐inf ‐inf Gly ‐0.01 1.09 1.76 0.42 Gly 0.41 1.13 0.88 0.82
Ala ‐inf ‐inf ‐inf ‐inf Ala ‐inf ‐inf ‐inf ‐inf Ala ‐0.72 0.66 0.64 0.58 Ala 0.42 0.56 0.72 0.47
Val ‐inf ‐inf ‐inf ‐inf Val ‐inf ‐inf ‐inf ‐inf Val 0.57 ‐inf 0.14 ‐inf Val ‐0.56 0.13 ‐0.03 0.45
Ile ‐inf ‐inf ‐inf ‐inf Ile ‐inf ‐inf ‐inf ‐inf Ile ‐inf 0.33 ‐0.39 ‐0.45 Ile ‐0.40 ‐1.79 0.13 ‐0.78
Leu ‐inf ‐inf ‐inf ‐inf Leu ‐inf ‐inf ‐inf ‐inf Leu ‐inf ‐0.54 ‐0.56 ‐0.62 Leu ‐0.17 ‐0.02 0.41 0.15
Pro ‐inf ‐inf ‐inf ‐inf Pro ‐inf ‐inf ‐inf ‐inf Pro ‐0.36 ‐0.36 ‐0.38 ‐inf Pro ‐inf ‐inf ‐inf ‐inf
Cys ‐inf ‐inf ‐inf 0.27 Cys ‐0.53 ‐0.53 ‐0.15 ‐1.31 Cys ‐inf ‐inf ‐inf ‐inf Cys 0.52 0.92 ‐inf ‐inf
Met ‐inf ‐inf ‐inf ‐inf Met ‐inf ‐inf ‐inf ‐inf Met ‐inf ‐inf 1.03 0.97 Met ‐1.06 0.33 ‐0.39 0.65
Phe ‐inf ‐inf ‐inf ‐inf Phe ‐inf ‐inf ‐inf ‐inf Phe ‐inf 0.72 0.29 0.23 Phe ‐0.70 ‐0.01 ‐0.04 ‐0.50
Tyr ‐0.33 ‐inf ‐0.35 ‐0.57 Tyr 0.21 0.28 0.15 0.05 Tyr 0.00 0.70 ‐0.71 ‐inf Tyr ‐0.17 ‐0.73 ‐0.75 ‐1.10
Trp ‐inf ‐inf ‐1.26 ‐1.32 Trp ‐1.02 ‐0.73 ‐0.35 ‐0.13 Trp ‐inf 0.35 ‐inf ‐inf Trp ‐1.07 ‐0.38 ‐1.10 ‐1.16
Ser ‐0.52 ‐0.97 0.19 ‐0.61 Ser 0.09 ‐0.22 0.23 0.42 Ser ‐0.64 0.05 0.59 ‐0.73 Ser ‐0.05 ‐0.05 0.35 0.45
Thr ‐0.83 0.06 ‐0.40 ‐0.67 Thr 0.03 ‐0.05 0.31 0.32 Thr 0.20 ‐0.09 ‐0.52 ‐0.58 Thr 0.52 0.16 0.19 0.63
Asn 0.73 0.17 0.74 0.68 Asn ‐0.44 ‐0.65 ‐0.02 ‐0.14 Asn ‐0.33 1.18 0.57 ‐1.11 Asn ‐0.36 ‐0.50 0.02 0.41
Gln 1.15 ‐0.11 0.50 0.09 Gln ‐0.20 ‐0.20 ‐0.13 ‐0.39 Gln ‐inf 0.37 0.35 ‐inf Gln 0.34 ‐0.76 0.22 0.25
Asp ‐0.59 1.55 0.49 ‐1.37 Asp ‐inf ‐inf ‐inf ‐inf Asp 0.30 1.00 ‐0.41 0.22 Asp ‐0.71 ‐0.72 0.11 ‐0.51
Glu ‐0.70 1.55 ‐0.32 ‐1.07 Glu ‐inf ‐2.97 ‐inf ‐inf Glu ‐inf 0.20 ‐0.52 ‐0.58 Glu ‐1.92 ‐inf 0.00 ‐0.62
His ‐1.31 ‐0.40 1.30 ‐0.15 His 0.16 0.25 0.45 0.74 His ‐inf 0.96 ‐inf 0.19 His ‐0.46 ‐0.75 ‐0.08 ‐0.32
Arg ‐0.14 ‐0.01 1.78 0.66 Arg 0.78 0.82 0.94 0.79 Arg 0.28 ‐0.53 ‐0.84 ‐0.40 Arg ‐1.04 ‐0.35 ‐0.66 ‐0.54
Lys ‐0.57 ‐1.56 1.12 0.12 Lys 0.67 0.88 0.76 0.77 Lys ‐inf 0.80 ‐0.69 ‐1.85 Lys 0.25 0.18 ‐0.32 ‐0.09
Figure 5. A flowchart of calculating the score of protein-DNA complex.
Figure 6. The flowchart of scanning CRP binding sites. We use the protein–DNA complex of CRP (PDB entry: 1zrc), to test the capacity of our model to discriminate targets within real CRP binding sequences.
(A)
(B)
Figure 7. The propensity of 20 amino acids in protein-DNA interaction. (A) Classify with interaction group. (B)Classify with interaction force.
0.00
Gly Ala Val Ile Leu Pro Cys Met Phe Tyr Trp Ser Thr Asn Gln Asp Glu His Arg Lys
Side
Gly Ala Val Ile Leu Pro Cys Met Phe Tyr Trp Ser Thr Asn Gln Asp Glu His Arg Lys
vdW Special
(A)
(B)
Figure 8. Distribution of interaction types of protein-DNA interactions. (A)In van der Waals forces. (B) In special-forces.
Vsm, 44%
Vss, 25%
Vms, 7%
Vmm, 24% Vsm
Vss Vms Vmm
Ssm, 54%
Sss, 22%
Sms, 5%
Smb, 19% Ssm
Sss Sms Smb
Figure 9. Evaluation of the scoring function in binding affinities prediction. The correlation between scoring matrices and experimental free
energy change (ΔΔG). Our scoring matrices were noted in orange diamonds and DBD-Hunter were green squares. The correlation of our method is -0.498 and DBD-Hunter is -0.471.
‐20
‐15
‐10
‐5 0 5 10
‐3 ‐2 ‐1 0 1 2 3 4 5
DBD‐Hunter This study
Figure 10. The distribution of distance from TFBSs to transcription start site (TSS).
(A)
(B)
(C)
Figure 11. Sequences logo of three kinds CRP regulator. (A) 197 activator binding sites, (B) 60 repressor binding sites, and (C) 16 dual binding sites.
6 7 8 9 11 12 13 13 14 14 15 15 16 16 17 18
R180 ss+sb ss/ss ss ss ss
E181 ss ss ss ss/ss ss
(A)
(B)
Figure 13. Sequences logos of scanning CRP binding sites result. (A) 97 TFBSs with ranking top 1%. (B) Least 50% of 9 TFBSs.