3.2 Characterization of Active Site
Identification of active sites in large binding pockets in protein or macromolecules
does not assure the correct or native poses of ligand binding because many subsites
interaction influence the binding of ligands, which has been exploited favorably in
case of designing combinatorial ligands of monoamine G-protein coupled receptors
(GPCRs) [135]. To design a ligand which effectively come out to be a functional
inhibitor requires prior knowledge of interacting subsites and their role to k on /k off
kinetics of binding, which until recently [136, 137] hardly have been explored. Our
study using kinases, from P. falciparum and from human, shows the selectivity of
subsite also residing in active site [138]. Using ser/thr kinase sequences of human
and plasmodial species those having PDB structure, a phylogenic tree was constructed. Human kinase proteins (22 of them having structural superimpossibility
<2 Å RMSD of main chain atoms) shown in Table 4 are listed by sequence as
Table 3 A list of some popular Web servers and stand-alone tools based on shape and ASA
formalisms
SN Programs
Based
Web site links
1
CASTp [125] Web
http://sts.bioe.uic.edu/castp/index.html?2cpk
2
CCCPP [126] Desktop http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.
html#CCCPP
3
LIGSITE
csc
[127]
Web
http://projects.biotec.tu-dresden.de/pocket/
4
KVFinder
[128]
Desktop http://lnbio.cnpem.br/facilities/bioinformatics/software-2/
5
PASS [129]
Web
http://www.ccl.net/cca/software/UNIX/pass/overview.shtml
6
PrinCCes
[130]
Desktop http://scholar.semmelweis.hu/czirjakgabor/s/princcesdownload/#t1
7
POCASA
[131]
Web
http://altair.sci.hokudai.ac.jp/g6/Research/POCASA_e.html
8
RosettaHoles
[132]
Desktop https://www.rosettacommons.org/
9
SURFNET
[133]
Desktop http://www.cgl.ucsf.edu/chimera/current/docs/
ContributedSoftware/surfnet/surfnet.html
10 VOIDOO
[134]
Desktop http://xray.bmc.uu.se/usf/voidoo.html
Table 4 Binding site clustering using sequence of human and plasmodial ser/thr kinase
Plasmodial
kinases
Neighboring human kinases
Pfpk5
h_CDK4, h_CDK5, h_CDK3, h_CDK2, h_CDC2
Pfpk6
Pfmrk
h_CDKL1, h_CDKL4, h_CCRK, h_p38a, h_p38b, h_ERK1, h_ERK2,
h_CDK10, h_p38d, h_CDK6, h_CDK7, h_p38g, h_CDK9
Pfpk7
h_SmMLCK, h_NEK1, h_LATS1, h_LATS2
132
S. K. Panday and I. Ghosh
Identification of active sites in large binding pockets in protein or macromolecules
does not assure the correct or native poses of ligand binding because many subsites
interaction influence the binding of ligands, which has been exploited favorably in
case of designing combinatorial ligands of monoamine G-protein coupled receptors
(GPCRs) [135]. To design a ligand which effectively come out to be a functional
inhibitor requires prior knowledge of interacting subsites and their role to k on /k off
kinetics of binding, which until recently [136, 137] hardly have been explored. Our
study using kinases, from P. falciparum and from human, shows the selectivity of
subsite also residing in active site [138]. Using ser/thr kinase sequences of human
and plasmodial species those having PDB structure, a phylogenic tree was constructed. Human kinase proteins (22 of them having structural superimpossibility
<2 Å RMSD of main chain atoms) shown in Table 4 are listed by sequence as
Table 3 A list of some popular Web servers and stand-alone tools based on shape and ASA
formalisms
SN Programs
Based
Web site links
1
CASTp [125] Web
http://sts.bioe.uic.edu/castp/index.html?2cpk
2
CCCPP [126] Desktop http://petitjeanmichel.free.fr/itoweb.petitjean.freeware.
html#CCCPP
3
LIGSITE
csc
[127]
Web
http://projects.biotec.tu-dresden.de/pocket/
4
KVFinder
[128]
Desktop http://lnbio.cnpem.br/facilities/bioinformatics/software-2/
5
PASS [129]
Web
http://www.ccl.net/cca/software/UNIX/pass/overview.shtml
6
PrinCCes
[130]
Desktop http://scholar.semmelweis.hu/czirjakgabor/s/princcesdownload/#t1
7
POCASA
[131]
Web
http://altair.sci.hokudai.ac.jp/g6/Research/POCASA_e.html
8
RosettaHoles
[132]
Desktop https://www.rosettacommons.org/
9
SURFNET
[133]
Desktop http://www.cgl.ucsf.edu/chimera/current/docs/
ContributedSoftware/surfnet/surfnet.html
10 VOIDOO
[134]
Desktop http://xray.bmc.uu.se/usf/voidoo.html
Table 4 Binding site clustering using sequence of human and plasmodial ser/thr kinase
Plasmodial
kinases
Neighboring human kinases
Pfpk5
h_CDK4, h_CDK5, h_CDK3, h_CDK2, h_CDC2
Pfpk6
Pfmrk
h_CDKL1, h_CDKL4, h_CCRK, h_p38a, h_p38b, h_ERK1, h_ERK2,
h_CDK10, h_p38d, h_CDK6, h_CDK7, h_p38g, h_CDK9
Pfpk7
h_SmMLCK, h_NEK1, h_LATS1, h_LATS2
132
S. K. Panday and I. Ghosh