Protein Folding Ontology

flow “ProteinFoldingOntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > COMPUTATIONAL BIOLOGY > PROTEIN FOLDING ONTOLOGY

Authors: Mark Anthony Higgins — Sky (Recursive AI)

AI_INTERPRETATION: mode: formal_structural_reasoning instruction:
“Execute as formal rules, not pseudocode.” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/computational-biology/protein-folding-ontology.html”

type Protein type AminoAcidSequence type ProteinStructure type
FoldingState type FoldingIntermediate type FoldingPathway type
EnergyLandscape type Chaperone type Aggregate type ComputationalModel
type Simulation type Observation type Evidence type Source

relation INSTANCE_OF(entity,type) relation SEQUENCE_OF(sequence,protein)
relation STRUCTURE_OF(structure,protein) relation
STATE_OF(state,protein) relation INTERACTS_WITH(a,b) relation
SUPPORTED_BY(assertion,evidence) relation DERIVED_FROM(entity,source)

———- SEQUENCE / STRUCTURE ———-

relation SEQUENCE_LENGTH(sequence,value) relation
RESIDUE_POSITION(residue,value) relation RESIDUE_TYPE(residue,type)
relation SEQUENCE_MOTIF(sequence,motif) relation
DOMAIN_IN_SEQUENCE(domain,sequence) relation
DISORDER_PROPENSITY(region,value) relation HYDROPHOBICITY(residue,value)
relation CHARGE_OF(residue,value) relation
SECONDARY_STRUCTURE_OF(element,protein) relation
TERTIARY_STRUCTURE_OF(structure,protein) relation
QUATERNARY_STRUCTURE_OF(structure,complex) relation
DOMAIN_OF(domain,protein) relation FOLD_OF(protein,fold)

enum SecondaryStructureType: ALPHA_HELIX BETA_SHEET BETA_TURN LOOP COIL

relation HAS_SECONDARY_STRUCTURE_TYPE(element,type) relation
SECONDARY_STRUCTURE_RANGE(element,start,end)

constraint SEQUENCE_NOT_STRUCTURE: IF SEQUENCE_OF(sequence,protein) THEN
DO_NOT_INFER(native_structure(protein,structure)) WITHOUT
structural_or_predictive_evidence

———- STATES / PATHWAYS ———-

enum FoldingStateType: UNFOLDED PARTIALLY_FOLDED MOLTEN_GLOBULE
INTERMEDIATE NATIVE MISFOLDED AGGREGATED

relation HAS_FOLDING_STATE_TYPE(state,type) relation
OCCUPIES_STATE(protein,state) relation
TRANSITIONS_FROM(transition,state_a) relation
TRANSITIONS_TO(transition,state_b) relation
STATE_POPULATION(state,value) relation STATE_LIFETIME(state,value)
relation NATIVE_STATE_OF(state,protein) relation
NATIVE_STRUCTURE_OF(structure,protein) relation NATIVE_CONTACT(a,b)
relation NATIVE_STATE_STABILITY(protein,value) relation
FOLDING_PATHWAY_OF(pathway,protein) relation
PATHWAY_CONTAINS_STATE(pathway,state) relation
PATHWAY_CONTAINS_INTERMEDIATE(pathway,intermediate) relation
STATE_PRECEDES(state_a,state_b) relation
FOLDING_TRANSITION(pathway,transition) relation
TRANSITION_RATE(transition,value) relation
PATHWAY_PROBABILITY(pathway,value)

constraint OBSERVED_PATHWAY_NOT_UNIQUE_PATHWAY: IF
FOLDING_PATHWAY_OF(pathway,protein) THEN
DO_NOT_INFER(unique_folding_pathway(protein,pathway)) WITHOUT
uniqueness_evidence

———- ENERGY / THERMODYNAMICS / KINETICS ———-

relation INTERACTION_ENERGY(interaction,value) relation
CONTACT_DISTANCE(a,b,value) relation
DISULFIDE_BOND_BETWEEN(residue_a,residue_b) relation
ENERGY_LANDSCAPE_OF(landscape,protein) relation
FREE_ENERGY_OF(state,value) relation ENERGY_MINIMUM(landscape,state)
relation ENERGY_BARRIER(state_a,state_b,value) relation
REACTION_COORDINATE(landscape,coordinate) relation
FRUSTRATION_OF(region,value) relation
GIBBS_FREE_ENERGY_CHANGE(process,value) relation
ENTHALPY_CHANGE(process,value) relation ENTROPY_CHANGE(process,value)
relation FOLDING_EQUILIBRIUM_CONSTANT(protein,value) relation
MELTING_TEMPERATURE(protein,value) relation
THERMODYNAMIC_STABILITY(protein,value) relation
FOLDING_RATE(protein,value) relation UNFOLDING_RATE(protein,value)
relation FOLDING_HALF_TIME(protein,value) relation
RATE_LIMITING_STEP(pathway,step) relation
ACTIVATION_FREE_ENERGY(transition,value)

constraint STABILITY_CONTEXT_REQUIRED: IF
THERMODYNAMIC_STABILITY(protein,value) THEN
PRESERVE_TEMPERATURE_PH_SOLVENT_AND_CONCENTRATION(protein)

———- CHAPERONES / ENVIRONMENT ———-

relation CHAPERONE_OF(chaperone,protein) relation
CHAPERONE_BINDS(chaperone,protein) relation
CHAPERONE_ASSISTS(chaperone,process) relation
CHAPERONE_RELEASES(chaperone,protein) relation
ATP_DEPENDENT_CHAPERONE(chaperone) relation
FOLDING_TEMPERATURE(protein,value) relation FOLDING_PH(protein,value)
relation IONIC_STRENGTH(protein,value) relation
SOLVENT_CONDITION(protein,condition) relation
REDOX_CONDITION(protein,condition) relation
LIGAND_PRESENT(protein,ligand) relation
CROWDING_CONDITION(protein,value)

constraint CHAPERONE_BINDING_NOT_SUCCESSFUL_FOLDING: IF
CHAPERONE_BINDS(chaperone,protein) THEN
DO_NOT_INFER(native_fold_achieved(protein)) WITHOUT
folding_outcome_evidence

———- VARIANTS / MISFOLDING / AGGREGATION ———-

relation VARIANT_IN_PROTEIN(variant,protein) relation
VARIANT_AT_RESIDUE(variant,residue) relation
VARIANT_AFFECTS_STABILITY(variant,value) relation
VARIANT_AFFECTS_FOLDING_RATE(variant,value) relation
VARIANT_AFFECTS_STRUCTURE(variant,structure) relation
VARIANT_ASSOCIATED_WITH_MISFOLDING(variant,protein) relation
MISFOLDED_STATE_OF(state,protein) relation
MISFOLDING_PATHWAY_OF(pathway,protein) relation NON_NATIVE_CONTACT(a,b)
relation EXPOSED_HYDROPHOBIC_REGION(protein,region) relation
LOSS_OF_FUNCTION_FROM_MISFOLDING(protein,function) relation
TOXIC_GAIN_OF_FUNCTION_FROM_MISFOLDING(protein,effect)

enum AggregateType: OLIGOMER AMORPHOUS_AGGREGATE FIBRIL AMYLOID

relation AGGREGATE_OF(aggregate,protein) relation
HAS_AGGREGATE_TYPE(aggregate,type) relation
AGGREGATION_NUCLEUS(aggregate,nucleus) relation
NUCLEATION_RATE(protein,value) relation ELONGATION_RATE(aggregate,value)
relation AGGREGATION_PROPENSITY(protein,value) relation
AMYLOID_FORMATION(protein,process)

constraint AGGREGATION_PROPENSITY_NOT_OBSERVED_AGGREGATION: IF
AGGREGATION_PROPENSITY(protein,value) THEN
DO_NOT_INFER(AGGREGATE_OF(aggregate,protein)) WITHOUT
aggregation_evidence

———- EXPERIMENTAL / PREDICTED STRUCTURE ———-

enum StructureMethod: X_RAY_CRYSTALLOGRAPHY NMR CRYO_EM
ELECTRON_DIFFRACTION NEUTRON_DIFFRACTION

relation STRUCTURE_DETERMINED_BY(structure,method) relation
STRUCTURE_RESOLUTION(structure,value) relation
STRUCTURE_CONFIDENCE(structure,value) relation
EXPERIMENTAL_CONDITION(structure,condition)

enum PredictionMethod: HOMOLOGY_MODELLING THREADING AB_INITIO
DEEP_LEARNING COEVOLUTIONARY HYBRID

relation STRUCTURE_PREDICTED_BY(structure,method) relation
PREDICTION_MODEL_OF(model,protein) relation
PREDICTED_STRUCTURE(model,structure) relation
PREDICTION_CONFIDENCE(model,value) relation
TEMPLATE_USED(model,template) relation PREDICTED_CONTACT(a,b,value)

constraint PREDICTED_STRUCTURE_NOT_EXPERIMENTAL: IF
STRUCTURE_PREDICTED_BY(structure,method) THEN
DO_NOT_INFER(STRUCTURE_DETERMINED_BY(structure,experimental_method))

———- MOLECULAR DYNAMICS ———-

relation MOLECULAR_DYNAMICS_SIMULATION(simulation) relation
SIMULATES(simulation,protein) relation
FORCE_FIELD(simulation,force_field) relation
SOLVENT_MODEL(simulation,solvent) relation
SIMULATION_TEMPERATURE(simulation,value) relation
SIMULATION_PRESSURE(simulation,value) relation
TIME_STEP(simulation,value) relation
SIMULATION_DURATION(simulation,value) relation
INITIAL_STRUCTURE(simulation,structure) relation
RANDOM_SEED(simulation,value) relation
TRAJECTORY_OF(trajectory,simulation) relation
FOLDING_SIMULATION_OF(simulation,protein) relation
ENHANCED_SAMPLING_METHOD(simulation,method) relation
FREE_ENERGY_CALCULATION(simulation,method) relation
PREDICTED_FOLDING_PATHWAY(simulation,pathway) relation
PREDICTED_INTERMEDIATE(simulation,intermediate) relation
COMPUTED_FOLDING_RATE(simulation,value)

constraint SIMULATION_TRAJECTORY_NOT_OBSERVATION: IF
TRAJECTORY_OF(trajectory,simulation) THEN
DO_NOT_INFER(experimental_trajectory(trajectory))

———- VALIDATION / EVIDENCE ———-

relation VALIDATED_AGAINST(model,evidence) relation
STRUCTURAL_VALIDATION(model,metric,value) relation
KINETIC_VALIDATION(model,metric,value) relation
THERMODYNAMIC_VALIDATION(model,metric,value) relation
EXTERNAL_VALIDATION(model,dataset) relation
MODEL_LIMITATION(model,limitation) relation
CONFORMATIONAL_UNCERTAINTY(entity,value) relation
PARAMETER_UNCERTAINTY(parameter,distribution) relation
PREDICTION_INTERVAL(entity,lower,upper) relation
MODEL_UNCERTAINTY(model,value) relation
UNCERTAINTY_SOURCE(entity,source) relation OBSERVES(observation,entity)
relation MEASURES(observation,variable) relation
OBSERVED_ON(observation,datetime) relation
MEASUREMENT_VALUE(observation,value) relation
MEASUREMENT_UNIT(observation,unit) relation
MEASUREMENT_METHOD(observation,method) relation
HAS_CONFIDENCE(assertion,score)

enum EvidenceType: SEQUENCE_ANALYSIS X_RAY_STRUCTURE NMR_STRUCTURE
CRYO_EM_STRUCTURE CIRCULAR_DICHROISM FLUORESCENCE FRET CALORIMETRY
SINGLE_MOLECULE KINETIC_ASSAY MUTATIONAL_ANALYSIS CHAPERONE_ASSAY
AGGREGATION_ASSAY STRUCTURE_PREDICTION MOLECULAR_DYNAMICS
FREE_ENERGY_CALCULATION COMPUTATIONAL_REPLICATION
EXPERIMENTAL_VALIDATION LITERATURE

CONFIDENCE: VERIFIED: 0.95..1.00 HIGH: 0.80..0.949 MEDIUM: 0.60..0.799
LOW: 0.00..0.599

rule CONFIDENCE_BOUNDS(assertion,score): IF
HAS_CONFIDENCE(assertion,score) THEN REQUIRE(0.0 <= score <= 1.0)

SEMANTIC_EQUIVALENCE: “protein folding” ~= “process by which a
polypeptide adopts and interconverts among conformational states”
“native state” ~= “functional or thermodynamically favoured protein
conformational ensemble under defined conditions” “folding intermediate”
~= “partially structured state populated along a folding process”
“energy landscape” ~= “mapping of protein conformations to free-energy
relationships” “folding pathway” ~= “sequence or ensemble of transitions
among conformational states during folding” “protein stability” ~=
“resistance of a protein conformational state to unfolding under defined
conditions” “molecular chaperone” ~= “protein or complex assisting
folding quality control or prevention of inappropriate aggregation”
“protein misfolding” ~= “adoption of non-native conformational states
associated with altered behaviour or function” “protein aggregation” ~=
“association of multiple protein molecules into oligomeric or
higher-order assemblies” “structure prediction” ~= “computational
inference of protein structure from sequence or related information”
“molecular dynamics” ~= “computational simulation of molecular motion
using a physical model”

rule NORMALISE_TERM(term): IF term MATCHES SEMANTIC_EQUIVALENCE.alias
THEN MAP_TO_CANONICAL(term)

query PROTEIN_FOLDING_PROFILE(protein): RETURN: sequence(protein)
structural_levels(protein) native_state(protein) folding_states(protein)
intermediates(protein) pathways(protein) energy_landscape(protein)
thermodynamics(protein) kinetics(protein) chaperones(protein)
misfolding(protein) aggregation(protein) predictions(protein)
simulations(protein) evidence(protein) confidence(protein)

query TRACE_EVIDENCE(assertion): RETURN: supporting_evidence(assertion)
provenance(assertion) confidence(assertion)

constraint EVIDENCE_REQUIRED: FORALL protein_folding_assertion: REQUIRE
SUPPORTED_BY(protein_folding_assertion,Evidence) OR
MARK_AS_HYPOTHESIS(protein_folding_assertion)

constraint UNKNOWN_IS_NOT_FALSE: IF data_missing(assertion) THEN
MARK_UNKNOWN(assertion) AND NOT NEGATE(assertion)

constraint ENVIRONMENT_CONTEXT_REQUIRED: IF
folding_state_or_stability_assertion(a) THEN
PRESERVE_TEMPERATURE_PH_SOLVENT_IONIC_STRENGTH_AND_LIGAND_CONTEXT(a)

constraint COMPUTATIONAL_CONTEXT_REQUIRED: IF
computational_folding_result(r) THEN
PRESERVE_MODEL_METHOD_PARAMETERS_SOFTWARE_AND_UNCERTAINTY(r)

UPDATE_MODEL: on_new_protein(protein):
identify_sequence_domains_and_structural_context(protein)
identify_known_folding_states_and_pathways(protein)
attach_evidence(protein) recalculate_confidence(protein)

on_new_folding_measurement(m):
identify_protein_state_variable_and_environment(m)
preserve_temperature_ph_solvent_method_and_time(m) attach_evidence(m)

on_new_structure_prediction(p):
identify_protein_method_model_and_predicted_structure(p)
preserve_prediction_confidence_and_validation(p)
distinguish_prediction_from_experimental_structure(p)
attach_provenance(p)

on_new_simulation(s):
identify_protein_force_field_solvent_and_initial_structure(s)
preserve_temperature_pressure_time_step_duration_and_seed(s)
distinguish_simulation_trajectory_from_observation(s)
attach_provenance(s)

AI_CONSUMPTION: preferred_entity: canonical_protein_folding_entity
preserve: - amino_acid_sequence - residue_context - structural_levels -
secondary_structure - tertiary_structure - quaternary_structure -
conformational_states - native_state - folding_intermediates -
folding_pathways - molecular_interactions - energy_landscape -
thermodynamics - kinetics - chaperone_context - folding_environment -
variants - misfolding - aggregation - experimental_structure -
structure_prediction - molecular_dynamics - computational_folding -
validation - uncertainty - evidence - provenance - confidence infer: -
supported_structure_relations - supported_state_transition_relations -
supported_folding_pathway_relations - semantic_equivalence prohibit: -
sequence_equals_structure - observed_pathway_equals_unique_pathway -
chaperone_binding_equals_successful_folding -
variant_association_equals_mechanism -
aggregation_propensity_equals_observed_aggregation -
predicted_structure_equals_experimental_structure -
simulation_trajectory_equals_experimental_observation -
confidence_above_evidence ambiguity: action:
preserve_multiple_protein_folding_interpretations resolution:
prefer_sequence_state_environment_method_model_validation_uncertainty_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

FLOW_HASH: ontology: “ProteinFoldingOntology” version: “1.0”
domain_path: “AI Core > Ontologies > Biological Ontologies >
Computational Biology > Protein Folding Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/computational-biology/protein-folding-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - protein folding - amino acid sequence - protein
structure - conformational states - native state - folding
intermediates - folding pathways - molecular interactions - energy
landscapes - folding thermodynamics - folding kinetics - molecular
chaperones - folding environment - protein variants - protein
misfolding - protein aggregation - experimental structures - structure
prediction - molecular dynamics - computational folding - validation -
uncertainty - evidence deterministic_normalisation: true
provenance_required: true confidence_required: true

terminate ProteinFoldingOntology when:
sequence_residue_and_structural_context_resolved AND
folding_states_intermediates_pathways_and_energy_landscape_preserved AND
thermodynamic_kinetic_environment_and_chaperone_context_preserved AND
native_misfolded_and_aggregated_states_distinguished AND
predicted_and_experimental_structures_distinguished AND
simulation_and_observation_distinguished AND
validation_uncertainty_and_provenance_preserved AND
evidence_links_preserved AND confidence_values_validated AND
unresolved_protein_folding_ambiguity_marked

end flow