The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1994-06

AUTHORS

Hans-Joachim Böhm

ABSTRACT

A new simple empirical function has been developed that estimates the free energy of binding for a given protein-ligand complex of known 3D structure. The function takes into account hydrogen bonds, ionic interactions, the lipophilic protein-ligand contact surface and the number of rotatable bonds in the ligand. The dataset for the calibration of the function consists of 45 protein-ligand complexes. The new energy function reproduces the binding constants (ranging from 2.5·10-2 to 4·10-14 M, corresponding to binding energies between -9 and -76 kJ/mol) of the dataset with a standard deviation of 7.9 kJ/mol, corresponding to 1.4 orders of magnitude in binding affinity. The individual contributions to protein-ligand binding obtained from the scoring function are: ideal neutral hydrogen bond: -4.7 kJ/mol; ideal ionic interaction: -8.3 kJ/mol; lipophilic contact: -0.17 kJ/mol Å2; one rotatable bond in the ligand: +1.4 kJ/mol. The function also contains a constant contribution (+5.4 kJ/mol) which may be rationalized as loss of translational and rotational entropy. The function can be evaluated very fast and is therefore also suitable for application in a 3D database search or de novo ligand design program such as LUDI. More... »

PAGES

243-256

Journal

Related Patents

  • Beta-Fluoroethyl Thiourea Compounds And Use
  • Cytotoxic Compounds
  • Heterocyclic Nonnucleoside Inhibitors Of Reverse Transcriptase
  • Tubulin Polymerization Inhibitors; Antiproliferative And Antitumor Agents
  • Jak-3 Inhibitors For Treating Allergic Disorders
  • Phenethyl-5-Bromopyridylthiourea (Pbt) And Dihydroalkoxybenzyloxopyrimidine (Dabo) Derivatives Exhibiting Spermicidal Activity
  • Cytotoxic Compounds
  • Tubulin Binding Compounds (Cobra)
  • Phenethyl-5-Bromopyridlythiourea (Pbt) And Dihydroalkoxybenzyloxopyrimidine (Dbabo) Derivatives Exhibiting Spermicidal Activity
  • Three-Dimensional Structure Of Lipocalin-Type Prostaglandin D Synthase And Utilization Of The Same
  • Methods For Identifying A Molecule That May Bind To A Target Molecule
  • Therapeutic Compounds
  • Nonnucleoside Inhibitors Of Reverse Transcriptase, Composite Binding Pocket And Method For Use Thereof
  • Method And Apparatus For Analysis Of Molecular Configurations And Combinations
  • Also Inhibit Replication Of Retrovirus Such As Human Immunodeficiency Virus-1
  • R-Isomers Of Nonnucleoside Inhibitors
  • Therapeutic Use Of Jak-3 Inhibitors
  • Heterocyclic Nonnucleoside Inhibitors Of Reverse Transcriptase
  • Heterocyclic Nonnucleoside Inhibitors Of Reverse Transcriptase
  • Jak-3 Inhibitors For Treating Allergic Disorders
  • Administering To A Mammal Quinazoline Derivative For Therapy Of Organ Transplant Rejection
  • Anticancer Agents; Enzyme Inhibitor
  • Synthetic Spiroketal Pyranes As Potent Anti-Cancer Agents And Use
  • Jak-3 Inhibitors For Treating Allergic Disorders
  • Tyrosine Kinase Drugs
  • Jak-3 Inhibitors For Treating Allergic Disorders
  • Method Of Preparing A Modified Granulocyte Colony Stimulating Factor (G-Csf) With Reduced Immunogenicity
  • Jak-3 Inhibitors For Treating Allergic Disorders
  • Inhibitors Of The Egf-Receptor Tyrosine Kinase And Methods For Their Use
  • Antitumor Agents Or Antiproliferation Agents
  • Nonnucleoside Inhibitors Of Reverse Transcriptase, Composite Binding Pocket And Methods For Use Thereof
  • Nni For Treatment Of Multi-Drug Resistant Hiv
  • Inhibitors Of Non-Nucleoside Reverse Transcriptase And Multi-Drug Resistant Human Immunodeficiency Virus Reverse Transcriptase
  • Treating Leukemia And Lymphoma, Sunburn And Skin Cancer
  • Janus Kinase 3 (Jak3); Such As 4-(3'-5'-Dibromo-4'-Hydroxyphenyl)-Amino-6,7-Dimethoxyquinazoline For Inhibiting Proinflamatory Mediator Release
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/bf00126743

    DOI

    http://dx.doi.org/10.1007/bf00126743

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1012372842

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/7964925


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/03", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Chemical Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0306", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Physical Chemistry (incl. Structural)", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Binding Sites", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Hydrogen Bonding", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Ligands", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Chemical", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Structure", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Conformation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Software", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Thermodynamics", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Central Research, BASF AG, D-67056, Ludwigshafen, Germany", 
              "id": "http://www.grid.ac/institutes/grid.3319.8", 
              "name": [
                "Central Research, BASF AG, D-67056, Ludwigshafen, Germany"
              ], 
              "type": "Organization"
            }, 
            "familyName": "B\u00f6hm", 
            "givenName": "Hans-Joachim", 
            "id": "sg:person.01303574675.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01303574675.47"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/355371a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1007440157", 
              "https://doi.org/10.1038/355371a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/314235a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053524488", 
              "https://doi.org/10.1038/314235a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00126217", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022298567", 
              "https://doi.org/10.1007/bf00126217"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00124387", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049316994", 
              "https://doi.org/10.1007/bf00124387"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf01677044", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1038489619", 
              "https://doi.org/10.1007/bf01677044"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1994-06", 
        "datePublishedReg": "1994-06-01", 
        "description": "A new simple empirical function has been developed that estimates the free energy of binding for a given protein-ligand complex of known 3D structure. The function takes into account hydrogen bonds, ionic interactions, the lipophilic protein-ligand contact surface and the number of rotatable bonds in the ligand. The dataset for the calibration of the function consists of 45 protein-ligand complexes. The new energy function reproduces the binding constants (ranging from 2.5\u00b710-2 to 4\u00b710-14 M, corresponding to binding energies between -9 and -76 kJ/mol) of the dataset with a standard deviation of 7.9 kJ/mol, corresponding to 1.4 orders of magnitude in binding affinity. The individual contributions to protein-ligand binding obtained from the scoring function are: ideal neutral hydrogen bond: -4.7 kJ/mol; ideal ionic interaction: -8.3 kJ/mol; lipophilic contact: -0.17 kJ/mol \u00c52; one rotatable bond in the ligand: +1.4 kJ/mol. The function also contains a constant contribution (+5.4 kJ/mol) which may be rationalized as loss of translational and rotational entropy. The function can be evaluated very fast and is therefore also suitable for application in a 3D database search or de novo ligand design program such as LUDI.", 
        "genre": "article", 
        "id": "sg:pub.10.1007/bf00126743", 
        "isAccessibleForFree": false, 
        "isPartOf": [
          {
            "id": "sg:journal.1105375", 
            "issn": [
              "0928-2866", 
              "1573-9023"
            ], 
            "name": "Journal of Computer-Aided Molecular Design", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "3", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "8"
          }
        ], 
        "keywords": [
          "protein-ligand complexes", 
          "hydrogen bonds", 
          "ionic interactions", 
          "rotatable bonds", 
          "kJ/", 
          "neutral hydrogen bonds", 
          "protein-ligand binding", 
          "lipophilic contacts", 
          "empirical scoring function", 
          "rotational entropy", 
          "bonds", 
          "free energy", 
          "three-dimensional structure", 
          "ligands", 
          "complexes", 
          "orders of magnitude", 
          "constants", 
          "scoring functions", 
          "constant contribution", 
          "structure", 
          "standard deviation", 
          "\u00c52", 
          "LUDI", 
          "interaction", 
          "surface", 
          "affinity", 
          "energy function", 
          "binding", 
          "individual contributions", 
          "energy", 
          "simple empirical functions", 
          "contact surface", 
          "applications", 
          "database search", 
          "function", 
          "contact", 
          "contribution", 
          "entropy", 
          "empirical function", 
          "deviation", 
          "magnitude", 
          "design program", 
          "order", 
          "calibration", 
          "development", 
          "loss", 
          "dataset", 
          "number", 
          "new energy function", 
          "search", 
          "program"
        ], 
        "name": "The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure", 
        "pagination": "243-256", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1012372842"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1007/bf00126743"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "7964925"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1007/bf00126743", 
          "https://app.dimensions.ai/details/publication/pub.1012372842"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-09-02T15:47", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_247.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1007/bf00126743"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/bf00126743'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/bf00126743'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/bf00126743'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/bf00126743'


     

    This table displays all metadata directly associated to this object as RDF triples.

    168 TRIPLES      21 PREDICATES      91 URIs      78 LITERALS      16 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1007/bf00126743 schema:about N3cf7a58586454c73b643f75afe35f394
    2 N5e9fd1dbb55f49ad9849bc7f98c6f6e5
    3 N61582d9539cc47cba0466ed005c57076
    4 N6dd8c6a734ae4c539ae346adcd0e531b
    5 Ncd29d176f03d47b6a9949b9ade4d49cf
    6 Neced18fb38f84d02950b5e2c809f71b6
    7 Nf45c90220d1d493bbfcc0ed307b020c2
    8 Nf6f40c08356b4fc78ea0cb23c885c86b
    9 Nffebc0a4d220476a8a00220c93698996
    10 anzsrc-for:03
    11 anzsrc-for:0306
    12 schema:author Ne61ae442106a4038b4c8895df64b66e3
    13 schema:citation sg:pub.10.1007/bf00124387
    14 sg:pub.10.1007/bf00126217
    15 sg:pub.10.1007/bf01677044
    16 sg:pub.10.1038/314235a0
    17 sg:pub.10.1038/355371a0
    18 schema:datePublished 1994-06
    19 schema:datePublishedReg 1994-06-01
    20 schema:description A new simple empirical function has been developed that estimates the free energy of binding for a given protein-ligand complex of known 3D structure. The function takes into account hydrogen bonds, ionic interactions, the lipophilic protein-ligand contact surface and the number of rotatable bonds in the ligand. The dataset for the calibration of the function consists of 45 protein-ligand complexes. The new energy function reproduces the binding constants (ranging from 2.5·10-2 to 4·10-14 M, corresponding to binding energies between -9 and -76 kJ/mol) of the dataset with a standard deviation of 7.9 kJ/mol, corresponding to 1.4 orders of magnitude in binding affinity. The individual contributions to protein-ligand binding obtained from the scoring function are: ideal neutral hydrogen bond: -4.7 kJ/mol; ideal ionic interaction: -8.3 kJ/mol; lipophilic contact: -0.17 kJ/mol Å2; one rotatable bond in the ligand: +1.4 kJ/mol. The function also contains a constant contribution (+5.4 kJ/mol) which may be rationalized as loss of translational and rotational entropy. The function can be evaluated very fast and is therefore also suitable for application in a 3D database search or de novo ligand design program such as LUDI.
    21 schema:genre article
    22 schema:isAccessibleForFree false
    23 schema:isPartOf N0ae180528d4f47b3b393d500e8e892cb
    24 N6b5651a6046e41229a986f6e3743a262
    25 sg:journal.1105375
    26 schema:keywords LUDI
    27 affinity
    28 applications
    29 binding
    30 bonds
    31 calibration
    32 complexes
    33 constant contribution
    34 constants
    35 contact
    36 contact surface
    37 contribution
    38 database search
    39 dataset
    40 design program
    41 development
    42 deviation
    43 empirical function
    44 empirical scoring function
    45 energy
    46 energy function
    47 entropy
    48 free energy
    49 function
    50 hydrogen bonds
    51 individual contributions
    52 interaction
    53 ionic interactions
    54 kJ/
    55 ligands
    56 lipophilic contacts
    57 loss
    58 magnitude
    59 neutral hydrogen bonds
    60 new energy function
    61 number
    62 order
    63 orders of magnitude
    64 program
    65 protein-ligand binding
    66 protein-ligand complexes
    67 rotatable bonds
    68 rotational entropy
    69 scoring functions
    70 search
    71 simple empirical functions
    72 standard deviation
    73 structure
    74 surface
    75 three-dimensional structure
    76 Å2
    77 schema:name The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure
    78 schema:pagination 243-256
    79 schema:productId N95331809a56a4b209bb950d8cdc1fa5b
    80 Nac6b9d25513a443ca947a3f3f01becbe
    81 Nf1b883b0ceb04bc1853b89f68f4035c8
    82 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012372842
    83 https://doi.org/10.1007/bf00126743
    84 schema:sdDatePublished 2022-09-02T15:47
    85 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    86 schema:sdPublisher N74004c00a2b24948811fd1c5d83e556a
    87 schema:url https://doi.org/10.1007/bf00126743
    88 sgo:license sg:explorer/license/
    89 sgo:sdDataset articles
    90 rdf:type schema:ScholarlyArticle
    91 N0ae180528d4f47b3b393d500e8e892cb schema:issueNumber 3
    92 rdf:type schema:PublicationIssue
    93 N3cf7a58586454c73b643f75afe35f394 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    94 schema:name Thermodynamics
    95 rdf:type schema:DefinedTerm
    96 N5e9fd1dbb55f49ad9849bc7f98c6f6e5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    97 schema:name Models, Chemical
    98 rdf:type schema:DefinedTerm
    99 N61582d9539cc47cba0466ed005c57076 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    100 schema:name Protein Conformation
    101 rdf:type schema:DefinedTerm
    102 N6b5651a6046e41229a986f6e3743a262 schema:volumeNumber 8
    103 rdf:type schema:PublicationVolume
    104 N6dd8c6a734ae4c539ae346adcd0e531b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    105 schema:name Molecular Structure
    106 rdf:type schema:DefinedTerm
    107 N74004c00a2b24948811fd1c5d83e556a schema:name Springer Nature - SN SciGraph project
    108 rdf:type schema:Organization
    109 N95331809a56a4b209bb950d8cdc1fa5b schema:name pubmed_id
    110 schema:value 7964925
    111 rdf:type schema:PropertyValue
    112 Nac6b9d25513a443ca947a3f3f01becbe schema:name dimensions_id
    113 schema:value pub.1012372842
    114 rdf:type schema:PropertyValue
    115 Ncd29d176f03d47b6a9949b9ade4d49cf schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    116 schema:name Proteins
    117 rdf:type schema:DefinedTerm
    118 Ne61ae442106a4038b4c8895df64b66e3 rdf:first sg:person.01303574675.47
    119 rdf:rest rdf:nil
    120 Neced18fb38f84d02950b5e2c809f71b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    121 schema:name Hydrogen Bonding
    122 rdf:type schema:DefinedTerm
    123 Nf1b883b0ceb04bc1853b89f68f4035c8 schema:name doi
    124 schema:value 10.1007/bf00126743
    125 rdf:type schema:PropertyValue
    126 Nf45c90220d1d493bbfcc0ed307b020c2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    127 schema:name Binding Sites
    128 rdf:type schema:DefinedTerm
    129 Nf6f40c08356b4fc78ea0cb23c885c86b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Ligands
    131 rdf:type schema:DefinedTerm
    132 Nffebc0a4d220476a8a00220c93698996 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Software
    134 rdf:type schema:DefinedTerm
    135 anzsrc-for:03 schema:inDefinedTermSet anzsrc-for:
    136 schema:name Chemical Sciences
    137 rdf:type schema:DefinedTerm
    138 anzsrc-for:0306 schema:inDefinedTermSet anzsrc-for:
    139 schema:name Physical Chemistry (incl. Structural)
    140 rdf:type schema:DefinedTerm
    141 sg:journal.1105375 schema:issn 0928-2866
    142 1573-9023
    143 schema:name Journal of Computer-Aided Molecular Design
    144 schema:publisher Springer Nature
    145 rdf:type schema:Periodical
    146 sg:person.01303574675.47 schema:affiliation grid-institutes:grid.3319.8
    147 schema:familyName Böhm
    148 schema:givenName Hans-Joachim
    149 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01303574675.47
    150 rdf:type schema:Person
    151 sg:pub.10.1007/bf00124387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049316994
    152 https://doi.org/10.1007/bf00124387
    153 rdf:type schema:CreativeWork
    154 sg:pub.10.1007/bf00126217 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022298567
    155 https://doi.org/10.1007/bf00126217
    156 rdf:type schema:CreativeWork
    157 sg:pub.10.1007/bf01677044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1038489619
    158 https://doi.org/10.1007/bf01677044
    159 rdf:type schema:CreativeWork
    160 sg:pub.10.1038/314235a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053524488
    161 https://doi.org/10.1038/314235a0
    162 rdf:type schema:CreativeWork
    163 sg:pub.10.1038/355371a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007440157
    164 https://doi.org/10.1038/355371a0
    165 rdf:type schema:CreativeWork
    166 grid-institutes:grid.3319.8 schema:alternateName Central Research, BASF AG, D-67056, Ludwigshafen, Germany
    167 schema:name Central Research, BASF AG, D-67056, Ludwigshafen, Germany
    168 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...