HARP Hansen's Disease Antimicrobial Resistance Profiles
Leprosy antimicrobial resistance Structure-based predictions Open access

Hansen's Disease Antimicrobial Resistance Profiles

HARP: Predicted Structural Impacts of Antimicrobial Resistance Mutations in Mycobacterium leprae

HARP is an integrated web resource that predicts how systematic missense mutations in the drug targets of Mycobacterium leprae affect protein structure. It brings together sequence- and structure-based predictions of changes in protein stability and vibrational entropy, and of protein–protein, protein–ligand and protein–nucleic acid affinities. HARP supports the mycobacterial research community in understanding how known and emerging mutations may lead to antimicrobial resistance in leprosy.

Browse mutations Search by drug Cite HARP
Structure of RNA polymerase (RNAP), the target of rifampicin Structure of dihydropteroate synthase (DHPS), the target of dapsone Structure of DNA gyrase (GYR), the target of ofloxacin
RNA polymerase (RNAP), the rifampicin target

HARP at a Glance

Every mutation in HARP carries the same 61 features, from residue properties to structure-based predictions.

80,902Mutations
61Features per mutation
4,935,022Annotations in total
4,258Residue positions
3 / 9Drug targets / protein chains
68Experimentally reported mutations

Drug Targets

Choose a drug to search for mutations in its target protein. Select a drug's structure to view it in PubChem.

Mutations and Features by Drug Target

All mutations in HARP, by drug target and protein chain, with the number of features recorded for each mutation.

Chain Gene Modelled Residues Residue Positions Mutations Features per Mutation Annotations
RifampicinRNA polymerase (RNAP) 6 chains 3,259 positions 61,921 mutations Search
A rpoA ML1957 3–226 224 4,256 61 259,616
B rpoA' ML1957 6–232 227 4,313 61 263,093
C rpoB ML1891 28–1153 1,126 21,394 61 1,305,034
D rpoC ML1890 3–1281 1,279 24,301 61 1,482,361
E rpoZ ML0542 28–108 81 1,539 61 93,879
F rpoT ML1022 253–574 322 6,118 61 373,198
DapsoneDihydropteroate synthase (DHPS) 1 chain 274 positions 5,206 mutations Search
A folP1 ML0224 5–278 274 5,206 61 317,566
OfloxacinDNA gyrase (GYR) 2 chains 725 positions 13,775 mutations Search
A gyrA ML0006 16–501 486 9,234 61 563,274
B gyrB ML0005 440–678 239 4,541 61 277,001
All Drug Targets 3 targets · 9 chains 4,258 80,902 61 4,935,022

Scroll sideways to see every column.

61 Features per Mutation

  • Wild-type residue properties5
  • Mutant residue properties11
  • Structure-based predictions22
  • Sequence-based predictions6
  • Vibrational entropy and energy terms17

Predicted Overall Impact

  • High impact 24,610 (30.4%)
  • Moderate impact 51,182 (63.3%)
  • Low impact 5,110 (6.3%)
Publication

Cite HARP

HARP: a database of structural impacts of systematic missense mutations in drug targets of Mycobacterium leprae

Vedithi SC, Malhotra S, Skwark MJ, Munir A, Acebrón-García-De-Eulate M, Waman VP, Alsulami A, Ascher DB, Blundell TL

Computational and Structural Biotechnology Journal, 2020. doi: 10.1016/j.csbj.2020.11.013