PMID- 29041842
OWN - NLM
STAT- MEDLINE
DCOM- 20180813
LR  - 20191210
IS  - 1532-4281 (Electronic)
IS  - 1079-9893 (Linking)
VI  - 38
IP  - 1
DP  - 2018 Feb
TI  - Identifying novel small molecule antagonists for mLST8 protein using 
      computational approaches.
PG  - 1-11
LID - 10.1080/10799893.2017.1387920 [doi]
AB  - Mammalian lethal with SEC13 protein 8 (mLST8), is an indispensable protein 
      subunit of mammalian target of rapamycin (mTOR) signaling pathway that interacts 
      with the kinase domain of mTOR protein, thereby stabilizing its active site. 
      Experimental studies reported the over expression of mLST8 in human colon and 
      prostate cancers by activation of both mTORC1/2 complexes and subsequent 
      downstream substrates leading to tumor progression. Considering its role, 
      targeting mLST8 protein would be a therapeutic approach against tumor progression 
      in colon and prostate cancers. Hence, using in silico structure based drug design 
      approach, the comparative binding patterns of 1,1'-binapthyl-2,2'diol (BINOL), 
      1-(2-carboxynaphth-1yl)-2-naphthoic acid (SCF-12) and their analogs in the cavity 
      of mLST8 were explored. ADME and binding energy calculations led to the 
      identification of five compounds with favorable Glide (G) scores and implicated 
      the importance of Asn132 and Gln225 as key binding residues. Molecular dynamics 
      (MD) simulations and free energy landscape (FEL) approaches helped in elucidating 
      the binding mechanism and suggested the possibility of ligands 1-3 namely, 
      ZINC01765622, ZINC62723702 and ZINC02576980 to be promising antagonists for 
      mLST8. Thus, this study substantiates the prospect of targeting mLST8 protein 
      using potent hits which could hinder tumor progression in colon and prostate 
      cancers.
FAU - Sapam, Tuleshwori Devi
AU  - Sapam TD
AD  - a Centre for Bioinformatics, School of Life Sciences , Pondicherry University , 
      Puducherry , India.
FAU - Velmurugan Ilavarasi, Anbumani
AU  - Velmurugan Ilavarasi A
AD  - a Centre for Bioinformatics, School of Life Sciences , Pondicherry University , 
      Puducherry , India.
FAU - Palaka, Bhagath Kumar
AU  - Palaka BK
AD  - a Centre for Bioinformatics, School of Life Sciences , Pondicherry University , 
      Puducherry , India.
FAU - Elumalai, Elakkiya
AU  - Elumalai E
AD  - a Centre for Bioinformatics, School of Life Sciences , Pondicherry University , 
      Puducherry , India.
FAU - Kanika, Nirmala Devi
AU  - Kanika ND
AD  - b Department of Biochemistry , S.V. University , Tirupati , India.
FAU - Ampasala, Dinakara Rao
AU  - Ampasala DR
AD  - a Centre for Bioinformatics, School of Life Sciences , Pondicherry University , 
      Puducherry , India.
LA  - eng
PT  - Journal Article
DEP - 20171017
PL  - England
TA  - J Recept Signal Transduct Res
JT  - Journal of receptor and signal transduction research
JID - 9509432
RN  - 0 (BINOL, naphthol)
RN  - 0 (Carboxylic Acids)
RN  - 0 (MLST8 protein, human)
RN  - 0 (Naphthalenes)
RN  - 0 (Naphthols)
RN  - 0 (mTOR Associated Protein, LST8 Homolog)
RN  - 2NIV4O66BH (1-naphthoic acid)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Carboxylic Acids/chemistry
MH  - Catalytic Domain/drug effects
MH  - Colonic Neoplasms/*drug therapy
MH  - Computer Simulation
MH  - Drug Design
MH  - Humans
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors/chemistry
MH  - Molecular Dynamics Simulation
MH  - Molecular Targeted Therapy
MH  - Naphthalenes/chemistry
MH  - Naphthols/*chemistry/pharmacology
MH  - Prostatic Neoplasms/*drug therapy
MH  - Protein Binding
MH  - Signal Transduction/drug effects
MH  - mTOR Associated Protein, LST8 Homolog/antagonists & inhibitors/*chemistry
OTO - NOTNLM
OT  - Colon cancer
OT  - free energy landscape
OT  - mLST8
OT  - mTOR
OT  - mTOR signaling pathway
OT  - molecular docking
OT  - molecular dynamics simulations
OT  - prostate cancer
EDAT- 2017/10/19 06:00
MHDA- 2018/08/14 06:00
CRDT- 2017/10/19 06:00
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2018/08/14 06:00 [medline]
PHST- 2017/10/19 06:00 [entrez]
AID - 10.1080/10799893.2017.1387920 [doi]
PST - ppublish
SO  - J Recept Signal Transduct Res. 2018 Feb;38(1):1-11. doi: 
      10.1080/10799893.2017.1387920. Epub 2017 Oct 17.