PMID- 23770402
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20130903
IS  - 1095-8541 (Electronic)
IS  - 0022-5193 (Linking)
VI  - 335
DP  - 2013 Oct 21
TI  - Charge density distribution and the electrostatic moments of CTPB in the active 
      site of p300 enzyme: a DFT and charge density study.
PG  - 119-29
LID - S0022-5193(13)00257-9 [pii]
LID - 10.1016/j.jtbi.2013.06.001 [doi]
AB  - A molecular docking and charge density analysis have been carried out to 
      understand the conformational change, charge distribution and electrostatic 
      properties of 
      N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide (CTPB) in 
      the active site of p300. The nearest neighbors, shortest intermolecular contacts 
      between CTPB-p300 and the lowest binding energy of CTPB have been analyzed from 
      the docking analysis. Further, a charge density analysis has been carried out for 
      the molecule in gas phase and for the corresponding molecule lifted from the 
      active site of p300. Due to the intermolecular interaction between CTPB and the 
      amino acids of active site, the conformation of the CTPB has been significantly 
      altered (particularly the pentadecyl chain). CTPB forms strong interaction with 
      the amino acid residues Tyr1397 and Trp1436 at the distance 2.12 and 2.72A, 
      respectively. However, the long pentadecyl alkyl chain of CTPB produces a barrier 
      and reducing the chance of forming hydrogen bonding with p300. The electron 
      density rhobcp(r) of the polar bonds (C-O, C-N, C-F and C-Cl) of CTPB are increased 
      when it present in the active site. The dipole moment of CTPB in the active site 
      is significantly less (5.73D) when compared with the gas phase (8.16D) form. In 
      the gas phase structure, a large region of negative electrostatic potential (ESP) 
      is found at the vicinity of O(2) and CF3 group, which is less around the O(1) 
      atom. Whereas, in the active site, the negative ESP around the CF3 group is 
      decreased and increased at the O(1) and O(2)-atoms. The ESP modifications of CTPB 
      in the active site are mainly attributed to the effect of intermolecular 
      interaction. The gas phase and active site study insights the molecular 
      flexibility and the electrostatic properties of CTPB in the active site.
CI  - (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Devipriya, B
AU  - Devipriya B
AD  - Laboratory of Biocrystallography and Computational Molecular Biology, Department 
      of Physics, Periyar University, Salem 636011, India.
FAU - Kumaradhas, P
AU  - Kumaradhas P
LA  - eng
PT  - Journal Article
DEP - 20130613
PL  - England
TA  - J Theor Biol
JT  - Journal of theoretical biology
JID - 0376342
RN  - 0 (Benzamides)
RN  - 42HK56048U (Tyrosine)
RN  - 8DUH1N11BX (Tryptophan)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (EP300 protein, human)
SB  - IM
MH  - Benzamides/*chemistry
MH  - Catalytic Domain
MH  - E1A-Associated p300 Protein/*chemistry
MH  - Humans
MH  - *Molecular Docking Simulation
MH  - *Molecular Dynamics Simulation
MH  - Static Electricity
MH  - Tryptophan/chemistry
MH  - Tyrosine/chemistry
OTO - NOTNLM
OT  - Electrostatic potential
OT  - Intermolecular interactions
OT  - Molecular docking
OT  - Quantum chemical calculations
EDAT- 2013/06/19 06:00
MHDA- 2014/03/26 06:00
CRDT- 2013/06/18 06:00
PHST- 2012/11/17 00:00 [received]
PHST- 2013/03/21 00:00 [revised]
PHST- 2013/06/03 00:00 [accepted]
PHST- 2013/06/18 06:00 [entrez]
PHST- 2013/06/19 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
AID - S0022-5193(13)00257-9 [pii]
AID - 10.1016/j.jtbi.2013.06.001 [doi]
PST - ppublish
SO  - J Theor Biol. 2013 Oct 21;335:119-29. doi: 10.1016/j.jtbi.2013.06.001. Epub 2013 
      Jun 13.