PMID- 24253321
OWN - NLM
STAT- MEDLINE
DCOM- 20140721
LR  - 20211021
IS  - 0948-5023 (Electronic)
IS  - 0948-5023 (Linking)
VI  - 19
IP  - 12
DP  - 2013 Dec
TI  - QM-MM simulations on p53-DNA complex: a study of hot spot and rescue mutants.
PG  - 5545-59
LID - 10.1007/s00894-013-2042-2 [doi]
AB  - p53 is a transcription factor involved in the expression of a number of 
      downstream genes in response to genotoxic stress. It is activated through post 
      translation modifications in normal as well as cancerous cells. However, due to 
      mutations occurring in p53 in cancer cells it is not able to perform its function 
      of DNA binding which leads to cell proliferation. It is found to be mutated in 
      50% of the cancers. These mutations occur at a high frequency in the DNA binding 
      region of the p53. Among the known seven hot spot cancer mutations G245S, R249S, 
      and R273C have been studied here using quantum mechanics and molecular mechanics 
      (QM-MM) simulations. These mutations along with their experimentally proven 
      rescue mutations have also been included in the present work. A comparative study 
      of these cancer mutations along with wild type and their rescue mutations has 
      been performed. A computational measure based on the free energy changes 
      occurring in the binding of the p53 to the DNA has been presented. A correlation 
      between the DNA binding property and important interaction between p53 and DNA 
      has been observed for all the mutants. The keys residues which contribute to the 
      binding of p53 to DNA by forming crucial hydrogen bonds have also been discussed 
      in detail. A 30 ns simulation study was analyzed to observe the local structural 
      changes and DNA binding property of p53 in case of wild type, cancer and rescue 
      mutants.
FAU - Koulgi, Shruti
AU  - Koulgi S
AD  - Bioinformatics Group, Centre for Development of Advanced Computing (C-DAC), Pune 
      University Campus, Pune, India, 411 007.
FAU - Achalere, Archana
AU  - Achalere A
FAU - Sharma, Neeru
AU  - Sharma N
FAU - Sonavane, Uddhavesh
AU  - Sonavane U
FAU - Joshi, Rajendra
AU  - Joshi R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131121
PL  - Germany
TA  - J Mol Model
JT  - Journal of molecular modeling
JID - 9806569
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Binding Sites
MH  - Cell Proliferation
MH  - DNA/*genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Humans
MH  - Molecular Dynamics Simulation
MH  - Mutation
MH  - Neoplasms/etiology/*genetics
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Quantum Theory
MH  - Tumor Suppressor Protein p53/*genetics/metabolism
EDAT- 2013/11/21 06:00
MHDA- 2014/07/22 06:00
CRDT- 2013/11/21 06:00
PHST- 2013/07/04 00:00 [received]
PHST- 2013/10/21 00:00 [accepted]
PHST- 2013/11/21 06:00 [entrez]
PHST- 2013/11/21 06:00 [pubmed]
PHST- 2014/07/22 06:00 [medline]
AID - 10.1007/s00894-013-2042-2 [doi]
PST - ppublish
SO  - J Mol Model. 2013 Dec;19(12):5545-59. doi: 10.1007/s00894-013-2042-2. Epub 2013 
      Nov 21.