Skip to content
2000
Volume 26, Issue 10
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

Abstract

Introduction

The PICK1 PDZ domain has been identified as a potential drug target for neurological disorders. After many years of effort, a few inhibitors, such as TAT-C5 and mPD5, have been discovered experimentally to bind to the PDZ domain with a relatively high binding affinity. With the rapid growth of computational research, there is an urgent need for more efficient computational methods to design viable ligands that target proteins.

Methods

Recently, a newly developed program called AfDesign (part of ColabDesign) at https://github.com/sokrypton/ColabDesign), an open-source software built on AlphaFold, has been suggested to be capable of generating ligands that bind to targeted proteins, thus potentially facilitating the ligand development process. To evaluate the performance of this program, we explored its ability to target the PICK1 PDZ domain, given our current understanding of it. We found that the designated length of the ligand and the number of recycles play vital roles in generating ligands with optimal properties.

Results

Utilizing AfDesign with a sequence length of 5 for the ligand produced the highest comparable ligands to that of prior identified ligands. Moreover, these designed ligands displayed significantly lower binding energy compared to manually created sequences.

Conclusion

This work demonstrated that AfDesign can potentially be a powerful tool to facilitate the exploration of the ligand space for the purpose of targeting PDZ domains.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cpps/10.2174/0113892037316932240806102854
2024-08-21
2025-11-16

  • From This Site

    /content/journals/cpps/10.2174/0113892037316932240806102854
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. XuJ. XiaJ. Structure and function of PICK1.Neurosignals2006-200715419020110.1159/00009848217215589
     [Google Scholar]
  2. ThorsenT.S. MadsenK.L. RebolaN. RathjeM. AnggonoV. BachA. MoreiraI.S. Stuhr-HansenN. DyhringT. PetersD. BeumingT. HuganirR. WeinsteinH. MulleC. StrømgaardK. RønnL.C.B. GetherU. Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD.Proc. Natl. Acad. Sci. USA2010107141341810.1073/pnas.090222510720018661
     [Google Scholar]
  3. ElkinsJ.M. PapagrigoriouE. BerridgeG. YangX. PhillipsC. GileadiC. SavitskyP. DoyleD.A. Structure of PICK1 and other PDZ domains obtained with the help of self-binding C-terminal extensions.Protein Sci.200716468369410.1110/ps.06265750717384233
     [Google Scholar]
  4. PanL. WuH. ShenC. ShiY. JinW. XiaJ. ZhangM. Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.EMBO J.200726214576458710.1038/sj.emboj.760186017914463
     [Google Scholar]
  5. KennedyM. Origin of PDZ Origin of PDZ (DHR, GLGF) domains.Trends Biochem. Sci.199520935010.1016/S0968‑0004(00)89074‑X7482701
     [Google Scholar]
  6. MadsenK.L. ThorsenT.S. Rahbek-ClemmensenT. EriksenJ. GetherU. Protein interacting with C kinase 1 (PICK1) reduces reinsertion rates of interaction partners sorted to Rab11-dependent slow recycling pathway.J. Biol. Chem.201228715122931230810.1074/jbc.M111.29470222303009
     [Google Scholar]
  7. ReymondN. Garrido-UrbaniS. BorgJ.P. DubreuilP. LopezM. PICK-1: A scaffold protein that interacts with Nectins and JAMs at cell junctions.FEBS Lett.2005579102243224910.1016/j.febslet.2005.03.01015811349
     [Google Scholar]
  8. KundeS.A. RademacherN. ZiegerH. ShoichetS.A. Protein kinase C regulates scp;AMPA/scp; receptor auxiliary protein Shisa9/scp;CKAMP/scp;44 through interactions with neuronal scaffold scp;PICK/scp;1.FEBS Open Bio2017791234124510.1002/2211‑5463.1226128904854
     [Google Scholar]
  9. ErlendssonS. ThorsenT.S. VauquelinG. Ammendrup-JohnsenI. WirthV. MartinezK.L. TeilumK. GetherU. MadsenK.L. Mechanisms of PDZ domain scaffold assembly illuminated by use of supported cell membrane sheets.eLife20198e3918010.7554/eLife.3918030605082
     [Google Scholar]
  10. KarlsenM.L. ThorsenT.S. JohnerN. Ammendrup-JohnsenI. ErlendssonS. TianX. SimonsenJ.B. Høiberg-NielsenR. ChristensenN.M. KhelashviliG. StreicherW. TeilumK. VestergaardB. WeinsteinH. GetherU. ArlethL. MadsenK.L. Structure of dimeric and tetrameric complexes of the BAR domain protein PICK1 determined by small-angle X-ray scattering.Structure20152371258127010.1016/j.str.2015.04.02026073603
     [Google Scholar]
  11. ChristensenN.R. De LucaM. LeverM.B. RichnerM. HansenA.B. Noes-HoltG. JensenK.L. RathjeM. JensenD.B. ErlendssonS. BartlingC.R.O. Ammendrup-JohnsenI. PedersenS.E. SchönauerM. NissenK.B. MidtgaardS.R. TeilumK. ArlethL. SørensenA.T. BachA. StrømgaardK. MeehanC.F. VægterC.B. GetherU. MadsenK.L. A high-affinity, bivalent PDZ domain inhibitor complexes PICK 1 to alleviate neuropathic pain.EMBO Mol. Med.2020126e1124810.15252/emmm.20191124832352640
     [Google Scholar]
  12. MadsenK.L. EriksenJ. Milan-LoboL. HanD.S. NivM.Y. Ammendrup-JohnsenI. HenriksenU. BhatiaV.K. StamouD. SitteH.H. McMahonH.T. WeinsteinH. GetherU. Membrane localization is critical for activation of the PICK1 BAR domain.Traffic2008981327134310.1111/j.1600‑0854.2008.00761.x18466293
     [Google Scholar]
  13. HanleyJ.G. PICK1: A multi-talented modulator of AMPA receptor trafficking.Pharmacol. Ther.2008118115216010.1016/j.pharmthera.2008.02.00218353440
     [Google Scholar]
  14. StanG.F. ShoemarkD.K. AlibhaiD. HanleyJ.G. Ca 2 + regulates dimerization of the BAR domain protein PICK1 and consequent membrane curvature.Front. Mol. Neurosci.20221589373910.3389/fnmol.2022.89373935721319
     [Google Scholar]
  15. ShiY. YuJ. JiaY. PanL. ShenC. XiaJ. ZhangM. Redox-regulated lipid membrane binding of the PICK1 PDZ domain.Biochemistry201049214432443910.1021/bi100269t20426484
     [Google Scholar]
  16. PontingC.P. Evidence for PDZ domains in bacteria, yeast, and plants.Protein Sci.19976246446810.1002/pro.55600602259041651
     [Google Scholar]
  17. CaoM. XuJ. ShenC. KamC. HuganirR.L. XiaJ. PICK1-ICA69 heteromeric BAR domain complex regulates synaptic targeting and surface expression of AMPA receptors.J. Neurosci.20072747129451295610.1523/JNEUROSCI.2040‑07.200718032668
     [Google Scholar]
  18. ShiY. ZhangL. YuanJ. XiaoH. YangX. NiuL. Zinc binding site in PICK1 is dominantly located at the CPC motif of its PDZ domain.J. Neurochem.200810631027103410.1111/j.1471‑4159.2008.05434.x18429931
     [Google Scholar]
  19. XiaoH. ShiY. WangL. YuanJ. Protein-protein interaction between domains of PDZ and BAR from PICK1.Chem. Res. Chin. Univ.200723219119510.1016/S1005‑9040(07)60040‑3
     [Google Scholar]
  20. JinW. ShenC. JingL. ZhaX. XiaJ. PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner.Mol. Brain2010313910.1186/1756‑6606‑3‑3921176140
     [Google Scholar]
  21. CabralJ.H.M. PetosaC. SutcliffeM.J. RazaS. ByronO. PoyF. MarfatiaS.M. ChishtiA.H. LiddingtonR.C. Crystal structure of a PDZ domain.Nature1996382659264965210.1038/382649a08757139
     [Google Scholar]
  22. van HamM. HendriksW. PDZ domains-glue and guide.Mol. Biol. Rep.2003302698210.1023/A:102394170349312841577
     [Google Scholar]
  23. GallardoR. IvarssonY. SchymkowitzJ. RousseauF. ZimmermannP. Structural diversity of PDZ-lipid interactions.ChemBioChem201011445646710.1002/cbic.20090061620091728
     [Google Scholar]
  24. BoudinH. DoanA. XiaJ. ShigemotoR. HuganirR.L. WorleyP. CraigA.M. Presynaptic clustering of mGluR7a requires the PICK1 PDZ domain binding site.Neuron200028248549710.1016/S0896‑6273(00)00127‑611144358
     [Google Scholar]
  25. MadsenK.L. BeumingT. NivM.Y. ChangC. DevK.K. WeinsteinH. GetherU. Molecular determinants for the complex binding specificity of the PDZ domain in PICK1.J. Biol. Chem.200528021205392054810.1074/jbc.M50057720015774468
     [Google Scholar]
  26. StaudingerJ. LuJ. OlsonE.N. Specific interaction of the PDZ domain protein PICK1 with the COOH terminus of protein kinase C-α.J. Biol. Chem.199727251320193202410.1074/jbc.272.51.320199405395
     [Google Scholar]
  27. TurnerC. De LucaM. WolfheimerJ. HernandezN. MadsenK.L. SchmidtH.D. Administration of a novel high affinity PICK1 PDZ domain inhibitor attenuates cocaine seeking in rats.Neuropharmacology202016410790110.1016/j.neuropharm.2019.10790131805281
     [Google Scholar]
  28. SørensenA.T. RombachJ. GetherU. MadsenK.L. The scaffold protein PICK1 as a target in chronic pain.Cells2022118125510.3390/cells1108125535455935
     [Google Scholar]
  29. DevK.K. Making protein interactions druggable: Targeting PDZ domains.Nat. Rev. Drug Discov.20043121047105610.1038/nrd157815573103
     [Google Scholar]
  30. AnggonoV. Koç-SchmitzY. WidagdoJ. KormannJ. QuanA. ChenC.M. RobinsonP.J. ChoiS.Y. LindenD.J. PlomannM. HuganirR.L. PICK1 interacts with PACSIN to regulate AMPA receptor internalization and cerebellar long-term depression.Proc. Natl. Acad. Sci. USA201311034139761398110.1073/pnas.131246711023918399
     [Google Scholar]
  31. CitriA. BhattacharyyaS. MaC. MorishitaW. FangS. RizoJ. MalenkaR.C. Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression.J. Neurosci.20103049164371645210.1523/JNEUROSCI.4478‑10.201021147983
     [Google Scholar]
  32. SteinbergJ.P. TakamiyaK. ShenY. XiaJ. RubioM.E. YuS. JinW. ThomasG.M. LindenD.J. HuganirR.L. Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression.Neuron200649684586010.1016/j.neuron.2006.02.02516543133
     [Google Scholar]
  33. DevK.K. NakanishiS. HenleyJ.M. The PDZ domain of PICK1 differentially accepts protein kinase C-α and GluR2 as interacting ligands.J. Biol. Chem.200427940413934139710.1074/jbc.M40449920015247289
     [Google Scholar]
  34. StevensA.O. KazanI.C. OzkanB. HeY. Investigating the allosteric response of the PICK1 PDZ domain to different ligands with all-atom simulations.Protein Sci.20223112e447410.1002/pro.447436251217
     [Google Scholar]
  35. PerezJ.L. KhatriL. ChangC. SrivastavaS. OstenP. ZiffE.B. PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2.J. Neurosci.200121155417542810.1523/JNEUROSCI.21‑15‑05417.200111466413
     [Google Scholar]
  36. BjerggaardC. FogJ.U. HastrupH. MadsenK. LolandC.J. JavitchJ.A. GetherU. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions.J. Neurosci.200424317024703610.1523/JNEUROSCI.1863‑04.200415295038
     [Google Scholar]
  37. JensenK. L. SørensenG. DenckerD. OwensW. A. Rahbek-ClemmensenT. Brett LeverM. RunegaardA. H. Riis ChristensenN. WeikopP. WörtweinG. ICK1-deficient mice exhibit impaired response to cocaine and dysregulated dopamine homeostasis.eNeuro201853ENEURO.0422-0417
     [Google Scholar]
  38. WickensM.M. KirklandJ.M. KnouseM.C. McGrathA.G. BriandL.A. Sex-specific role for prefrontal cortical protein interacting with C kinase 1 in cue-induced cocaine seeking.Addict. Biol.2021265e1305110.1111/adb.1305134110073
     [Google Scholar]
  39. KimJ.E. LeeD.S. ParkH. KimT.H. KangT.C. Inhibition of AKT/GSK3β/CREB pathway improves the responsiveness to AMPA receptor antagonists by regulating gria1 surface expression in chronic epilepsy rats.Biomedicines20219442510.3390/biomedicines904042533919872
     [Google Scholar]
  40. DevK.K. HenleyJ.M. The schizophrenic faces of PICK1.Trends Pharmacol. Sci.2006271157457910.1016/j.tips.2006.09.00717011050
     [Google Scholar]
  41. SongA. GaoY. A potential drug target protein with diverse functions.Chin J Biochem Mol Biol20072309697705
     [Google Scholar]
  42. SongS. LiT. StevensA.O. RaadT. HeY. Investigating the mechanical properties and flexibility of N-BAR domains in PICK1 by molecular dynamics simulations.Curr. Protein Pept. Sci.2023241086587710.2174/138920372466623052209384237218192
     [Google Scholar]
  43. StevensA.O. HeY. Residue-level contact reveals modular domain interactions of PICK1 are driven by both electrostatic and hydrophobic forces.Front. Mol. Biosci.2021761613510.3389/fmolb.2020.61613533585564
     [Google Scholar]
  44. StevensA.O. LuoS. HeY. Three binding conformations of BIO124 in the pocket of the PICK1 PDZ domain.Cells20221115245110.3390/cells1115245135954295
     [Google Scholar]
  45. FocantM.C. HermansE. Protein interacting with C kinase and neurological disorders.Synapse201367853254010.1002/syn.2165723436724
     [Google Scholar]
  46. ChristensenN.R. ČalyševaJ. FernandesE.F.A. LüchowS. ClemmensenL.S. Haugaard-KedströmL.M. StrømgaardK. PDZ domains as drug targets.Adv. Ther.201927180014310.1002/adtp.20180014332313833
     [Google Scholar]
  47. GiallourakisC. CaoZ. GreenT. WachtelH. XieX. Lopez-IllasacaM. DalyM. RiouxJ. XavierR. A molecular-properties-based approach to understanding PDZ domain proteins and PDZ ligands.Genome Res.20061681056107210.1101/gr.528520616825666
     [Google Scholar]
  48. ErlendssonS. MadsenK. Membrane binding and modulation of the PDZ domain of PICK1.Membranes20155459761510.3390/membranes504059726501328
     [Google Scholar]
  49. BoliaA. GerekZ.N. KeskinO. Banu OzkanS. DevK.K. The binding affinities of proteins interacting with the PDZ domain of PICK1.Proteins20128051393140810.1002/prot.2403422275068
     [Google Scholar]
  50. PedersenS.W. PedersenS.B. AnkerL. HultqvistG. KristensenA.S. JemthP. StrømgaardK. Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations.Nat. Commun.201451321510.1038/ncomms421524477114
     [Google Scholar]
  51. ErnstA. AppletonB.A. IvarssonY. ZhangY. GfellerD. WiesmannC. SidhuS.S. A structural portrait of the PDZ domain family.J. Mol. Biol.2014426213509351910.1016/j.jmb.2014.08.01225158098
     [Google Scholar]
  52. CHAPTER 12 - Scaffolding proteins in transport regulation.Seldin and Giebisch's The KidneyFourth EdAcademic Press2008325341
     [Google Scholar]
  53. ChiC.N. BachA. StrømgaardK. GianniS. JemthP. Ligand binding by PDZ domains.Biofactors201238533834810.1002/biof.103122674855
     [Google Scholar]
  54. BezprozvannyI. MaximovA. Classification of PDZ domains.FEBS Lett.2001509345746210.1016/S0014‑5793(01)03214‑811749973
     [Google Scholar]
  55. HungA.Y. ShengM. PDZ domains: Structural modules for protein complex assembly.J. Biol. Chem.200227785699570210.1074/jbc.R10006520011741967
     [Google Scholar]
  56. DanielsD.L. CohenA.R. AndersonJ.M. BrüngerA.T. Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition.Nat. Struct. Biol.19985431732510.1038/nsb0498‑3179546224
     [Google Scholar]
  57. RomeroG. Von ZastrowM. FriedmanP.A. Role of PDZ proteins in regulating trafficking, signaling, and function of GPCRs: Means, motif, and opportunity.Pharmacology of G Protein Coupled Receptors.Elsevier201127931410.1016/B978‑0‑12‑385952‑5.00003‑8
     [Google Scholar]
  58. JensenKL Noes-HoltG SørensenAT MadsenKL A novel peripheral action of PICK1 inhibition in inflammatory pain.Front. Cell Neurosci20211575090210.3389/fncel.2021.750902
     [Google Scholar]
  59. BachA. Stuhr-HansenN. ThorsenT.S. BorkN. MoreiraI.S. FrydenvangK. PadrahS. ChristensenS.B. MadsenK.L. WeinsteinH. GetherU. StrømgaardK. Structure–activity relationships of a small-molecule inhibitor of the PDZ domain of PICK1.Org. Biomol. Chem.20108194281428810.1039/c0ob00025f20668766
     [Google Scholar]
  60. TsengY.L. LiuJ.J. HongR.L. Translocation of liposomes into cancer cells by cell-penetrating peptides penetratin and tat: A kinetic and efficacy study.Mol. Pharmacol.200262486487210.1124/mol.62.4.86412237333
     [Google Scholar]
  61. RoneyJ.P. OvchinnikovS. State-of-the-art estimation of protein model accuracy using alphafold.Phys. Rev. Lett.20221292323810110.1103/PhysRevLett.129.23810136563190
     [Google Scholar]
  62. AnishchenkoI. PellockS.J. ChidyausikuT.M. RamelotT.A. OvchinnikovS. HaoJ. BafnaK. NornC. KangA. BeraA.K. DiMaioF. CarterL. ChowC.M. MontelioneG.T. BakerD. De novo protein design by deep network hallucination.Nature2021600788954755210.1038/s41586‑021‑04184‑w34853475
     [Google Scholar]
  63. YehA.H.W. NornC. KipnisY. TischerD. PellockS.J. EvansD. MaP. LeeG.R. ZhangJ.Z. AnishchenkoI. CoventryB. CaoL. DauparasJ. HalabiyaS. DeWittM. CarterL. HoukK.N. BakerD. De novo design of luciferases using deep learning.Nature2023614794977478010.1038/s41586‑023‑05696‑336813896
     [Google Scholar]
  64. JeliazkovJ.R. Del AlamoD. KarpiakJ.D. ESMFold Hallucinates Native-Like Protein Sequences.Cold Spring Harbor Laboratory202310.1101/2023.05.23.541774
     [Google Scholar]
  65. KosugiT. OhueM. Solubility-aware protein binding peptide design using alphafold.Biomedicines2022107162610.3390/biomedicines10071626
     [Google Scholar]
  66. AnL. HicksD.R. ZorineD. DauparasJ. WickyB.I.M. MillesL.F. CourbetA. BeraA.K. NguyenH. KangA. CarterL. BakerD. Hallucination of closed repeat proteins containing central pockets.Nat. Struct. Mol. Biol.202330111755176010.1038/s41594‑023‑01112‑637770718
     [Google Scholar]
  67. WangJ. LisanzaS. JuergensD. TischerD. WatsonJ.L. CastroK.M. RagotteR. SaragoviA. MillesL.F. BaekM. AnishchenkoI. YangW. HicksD.R. ExpòsitM. SchlichthaerleT. ChunJ.H. DauparasJ. BennettN. WickyB.I.M. MuenksA. DiMaioF. CorreiaB. OvchinnikovS. BakerD. Scaffolding protein functional sites using deep learning.Science2022377660438739410.1126/science.abn210035862514
     [Google Scholar]
  68. WangW. PengZ. YangJ. Single-sequence protein structure prediction using supervised transformer protein language models.Nat. Comput. Sci.202221280481410.1038/s43588‑022‑00373‑338177395
     [Google Scholar]
  69. ZhangB. LiuK. ZhengZ. LiuY. MuJ. WeiT. ChenH-F. Protein Language Model Supervised Precise and Efficient Protein Backbone Design Method.Cold Spring Harbor Laboratory202310.1101/2023.10.26.564121
     [Google Scholar]
  70. DauparasJ. AnishchenkoI. BennettN. BaiH. RagotteR.J. MillesL.F. WickyB.I.M. CourbetA. de HaasR.J. BethelN. LeungP.J.Y. HuddyT.F. PellockS. TischerD. ChanF. KoepnickB. NguyenH. KangA. SankaranB. BeraA.K. KingN.P. BakerD. Robust deep learning–based protein sequence design using ProteinMPNN.Science20223786615495610.1126/science.add218736108050
     [Google Scholar]
  71. JensenK.L. ChistensenN.R. Noes-HoltG. KanneworffI.B. SivertsenL. BaroR.C. Jiménez-FernándezL. GoddardC.M. HopkinsC. ThomsenC.D. mPD5, an efficacious PICK1 inhibitor for treating chronic pain.bioRxiv20232023.2003.2003.530471
     [Google Scholar]
  72. LimongelliV. Ligand binding free energy and kinetics calculation in 2020.Wiley Interdiscip. Rev. Comput. Mol. Sci.2020104e145510.1002/wcms.1455
     [Google Scholar]
  73. GapsysV. MichielssensS. PetersJ.H. De GrootB.L. LeonovH. Calculation of binding free energies.Methods in Molecular Biology.Springer New York2015173209
     [Google Scholar]
  74. RoyU. LuckL.A. Molecular modeling of estrogen receptor using molecular operating environment.Biochem. Mol. Biol. Educ.200735423824310.1002/bmb.6521591100
     [Google Scholar]
  75. AlshargabiT.Q. SolimanS.M. ZakariaA. OsmanD.H. HagarM. AlshorifiF.T. MarieM.G. BarakatA. HaukkaM. AltowyanM.S. SawyM.A.E. Synthesis, X-ray structure, Hirshfeld, cytotoxicity and anticancer studies of pyrazole and pyridazin-4(H)-one derivatives.J. Mol. Struct.2024130413765410.1016/j.molstruc.2024.137654
     [Google Scholar]
  76. MahajanG. ChauhanV. SharmaV. GuptaR. Combining in vitro and in silico studies to unravel the antifungal potential of chitinase from a marine bacterial isolate Cellulosimicrobium cellulans RS7.Process Biochem.20231348810010.1016/j.procbio.2023.09.024
     [Google Scholar]
  77. XuL. ChenY. ShenT. LinC. ZhangB. Genetic analysis of PICK1 gene in alzheimer’s disease: A study for finding a new gene target.Front. Neurol.20199116910.3389/fneur.2018.0116930687223
     [Google Scholar]
  78. ChenY.T. LinC.H. HuangC.H. LiangW.M. LaneH.Y. PICK1 genetic variation and cognitive function in patients with schizophrenia.Sci. Rep.201771188910.1038/s41598‑017‑01975‑y28507309
     [Google Scholar]
  79. ReganL. CaballeroD. HinrichsenM.R. VirruetaA. WilliamsD.M. O’HernC.S. Protein design: Past, present, and future.Biopolymers2015104433435010.1002/bip.2263925784145
     [Google Scholar]
  80. HoS.P. DeGradoW.F. Design of a 4-helix bundle protein: Synthesis of peptides which self-associate into a helical protein.J. Am. Chem. Soc.1987109226751675810.1021/ja00256a032
     [Google Scholar]
  81. WermuthC.G. AldousD. RaboissonP. RognanD. The practice of medicinal chemistry.Elsevier Academic Press2015
     [Google Scholar]
  82. HarveyA. Natural products in drug discovery.Drug Discov. Today20081319-2089490110.1016/j.drudis.2008.07.00418691670
     [Google Scholar]
  83. MirditaM. SchützeK. MoriwakiY. HeoL. OvchinnikovS. SteineggerM. ColabFold: Making protein folding accessible to all.Nat. Methods202219667968210.1038/s41592‑022‑01488‑135637307
     [Google Scholar]
/content/journals/cpps/10.2174/0113892037316932240806102854
Loading
Utilizing AfDesign for Developing a Small Molecule Inhibitor of PICK1-PDZ
Curr. Protein Pept. Sci. 26, 861 (2025); https://doi.org/10.2174/0113892037316932240806102854
/content/journals/cpps/10.2174/0113892037316932240806102854
/content/journals/cpps/10.2174/0113892037316932240806102854
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): AfDesign; AlphaFold; ColabFold; inhibitor; PDZ; PICK1

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test