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PDBsum entry 3fc1

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protein ligands metals links
Transferase PDB id
3fc1
Jmol
Contents
Protein chain
334 a.a. *
Ligands
52P
Metals
_CL
Waters ×133
* Residue conservation analysis
PDB id:
3fc1
Name: Transferase
Title: Crystal structure of p38 kinase bound to pyrimido-pyridazino inhibitor
Structure: Mitogen-activated protein kinase 14. Chain: x. Synonym: mitogen-activated protein kinase p38 alpha, map ki alpha, cytokine suppressive anti-inflammatory drug-binding csaid-binding protein, csbp, max-interacting protein 2, map mxi2, sapk2a. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Gene: mapk14, csbp, csbp1, csbp2, cspb1, mxi2. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_variant: tn-368.
Resolution:
2.40Å     R-factor:   0.204     R-free:   0.251
Authors: M.D.Jacobs,S.Bellon
Key ref: D.A.Pearlman (2005). Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase. J Med Chem, 48, 7796-7807. PubMed id: 16302819
Date:
20-Nov-08     Release date:   09-Dec-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q16539  (MK14_HUMAN) -  Mitogen-activated protein kinase 14
Seq:
Struc:
360 a.a.
334 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.24  - Mitogen-activated protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell   8 terms 
  Biological process     intracellular signal transduction   70 terms 
  Biochemical function     nucleotide binding     11 terms  

 

 
    reference    
 
 
J Med Chem 48:7796-7807 (2005)
PubMed id: 16302819  
 
 
Evaluating the molecular mechanics poisson-boltzmann surface area free energy method using a congeneric series of ligands to p38 MAP kinase.
D.A.Pearlman.
 
  ABSTRACT  
 
The recently described molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method for calculating free energies is applied to a congeneric series of 16 ligands to p38 MAP kinase whose binding constants span approximately 2 orders of magnitude. These compounds have previously been used to test and compare other free energy calculation methods, including thermodynamic integration (TI), OWFEG, ChemScore, PLPScore, and Dock Energy Score. We find that the MM-PBSA performs relatively poorly for this set of ligands, yielding results much inferior to those from TI or OWFEG, inferior to Dock Energy Score, and not appreciably better than ChemScore or PLPScore but at an appreciably larger computational cost than any of these other methods. This suggests that one should be selective in applying the MM-PBSA method and that for systems that are amenable to other free energy approaches, these other approaches may be preferred. We also examine the single simulation approximation for MM-PBSA, whereby the required ligand and protein trajectories are extracted from a single MD simulation rather than two separate MD runs. This assumption, sometimes used to speed the MM-PBSA calculation, is found to yield significantly inferior results with only a moderate net percentage reduction in total simulation time.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21287607 J.M.Hayes, V.T.Skamnaki, G.Archontis, C.Lamprakis, J.Sarrou, N.Bischler, A.L.Skaltsounis, S.E.Zographos, and N.G.Oikonomakos (2011).
Kinetics, in silico docking, molecular dynamics, and MM-GBSA binding studies on prototype indirubins, KT5720, and staurosporine as phosphorylase kinase ATP-binding site inhibitors: the role of water molecules examined.
  Proteins, 79, 703-719.  
20949517 T.Hou, J.Wang, Y.Li, and W.Wang (2011).
Assessing the performance of the molecular mechanics/Poisson Boltzmann surface area and molecular mechanics/generalized Born surface area methods. II. The accuracy of ranking poses generated from docking.
  J Comput Chem, 32, 866-877.  
19916033 C.Obiol-Pardo, A.Cordero, J.Rubio-Martinez, and S.Imperial (2010).
Homology modeling of Mycobacterium tuberculosis 2C-methyl-D-erythritol-4-phosphate cytidylyltransferase, the third enzyme in the MEP pathway for isoprenoid biosynthesis.
  J Mol Model, 16, 1061-1073.  
20183853 D.D.Robinson, W.Sherman, and R.Farid (2010).
Understanding kinase selectivity through energetic analysis of binding site waters.
  ChemMedChem, 5, 618-627.  
21278915 J.Luccarelli, J.Michel, J.Tirado-Rives, and W.L.Jorgensen (2010).
Effects of Water Placement on Predictions of Binding Affinities for p38α MAP Kinase Inhibitors.
  J Chem Theory Comput, 6, 3850-3856.  
  20186976 N.Singh, and A.Warshel (2010).
Absolute binding free energy calculations: on the accuracy of computational scoring of protein-ligand interactions.
  Proteins, 78, 1705-1723.  
20730182 S.Y.Huang, S.Z.Grinter, and X.Zou (2010).
Scoring functions and their evaluation methods for protein-ligand docking: recent advances and future directions.
  Phys Chem Chem Phys, 12, 12899-12908.  
21152288 S.Y.Huang, and X.Zou (2010).
Advances and challenges in protein-ligand docking.
  Int J Mol Sci, 11, 3016-3034.  
20151417 V.Zoete, M.B.Irving, and O.Michielin (2010).
MM-GBSA binding free energy decomposition and T cell receptor engineering.
  J Mol Recognit, 23, 142-152.  
19368882 D.L.Mobley, and K.A.Dill (2009).
Binding of small-molecule ligands to proteins: "what you see" is not always "what you get".
  Structure, 17, 489-498.  
19356594 D.Xu, E.I.Newhouse, R.E.Amaro, H.C.Pao, L.S.Cheng, P.R.Markwick, J.A.McCammon, W.W.Li, and P.W.Arzberger (2009).
Distinct glycan topology for avian and human sialopentasaccharide receptor analogues upon binding different hemagglutinins: a molecular dynamics perspective.
  J Mol Biol, 387, 465-491.  
19405629 F.M.Ytreberg (2009).
Absolute FKBP binding affinities obtained via nonequilibrium unbinding simulations.
  J Chem Phys, 130, 164906.  
18781280 J.Kongsted, and U.Ryde (2009).
An improved method to predict the entropy term with the MM/PBSA approach.
  J Comput Aided Mol Des, 23, 63-71.  
18438971 C.Obiol-Pardo, J.M.Granadino-Roldán, and J.Rubio-Martinez (2008).
Protein-protein recognition as a first step towards the inhibition of XIAP and Survivin anti-apoptotic proteins.
  J Mol Recognit, 21, 190-204.  
18433285 T.Baştuğ, P.C.Chen, S.M.Patra, and S.Kuyucak (2008).
Potential of mean force calculations of ligand binding to ion channels from Jarzynski's equality and umbrella sampling.
  J Chem Phys, 128, 155104.  
17599350 D.L.Mobley, A.P.Graves, J.D.Chodera, A.C.McReynolds, B.K.Shoichet, and K.A.Dill (2007).
Predicting absolute ligand binding free energies to a simple model site.
  J Mol Biol, 371, 1118-1134.
PDB codes: 2oty 2otz 2ou0
17384076 E.L.Wu, Y.Mei, K.Han, and J.Z.Zhang (2007).
Quantum and molecular dynamics study for binding of macrocyclic inhibitors to human alpha-thrombin.
  Biophys J, 92, 4244-4253.  
17201676 M.K.Gilson, and H.X.Zhou (2007).
Calculation of protein-ligand binding affinities.
  Annu Rev Biophys Biomol Struct, 36, 21-42.  
17937781 O.A.Gani (2007).
Signposts of docking and scoring in drug design.
  Chem Biol Drug Des, 70, 360-365.  
17036304 C.S.Page, and P.A.Bates (2006).
Can MM-PBSA calculations predict the specificities of protein kinase inhibitors?
  J Comput Chem, 27, 1990-2007.  
16617086 E.Lyman, and D.M.Zuckerman (2006).
Ensemble-based convergence analysis of biomolecular trajectories.
  Biophys J, 91, 164-172.  
16758486 H.Alonso, A.A.Bliznyuk, and J.E.Gready (2006).
Combining docking and molecular dynamic simulations in drug design.
  Med Res Rev, 26, 531-568.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.