1. CDK5 NgR1
Asp 73 Arg 103
His 71 Arg 103, His 104
Ser 46 Pro 60
Ser 159 Ser 30
Arg 156 Thr 36
Arg 50 Ser 57
Arg 149 Pro 32, Cys 31
Insilco interaction prediction: An approach to define crosstalk
between essential bimolecular interactions in CNS perspective
Abhishek B. Jha*, Dr. Shital S. Panchal
Institute of Pharmacy, Nirma University, Ahmedabad-382481
References:
1.Azad, A. K. M., Lawen, A., & Keith, J. M. (2015). Predic-
tion of signaling cross-talks contributing to acquired drug
resistance in breast cancer cells by Bayesian statistical mod-
eling. BMC Systems Biology, 9(2), 1–17. http://
doi.org/10.1186/s12918-014-0135-x
2.Donaldson, R., & Calder, M. (2010). Modelling and Analy-
sis of Biochemical Signalling Pathway Cross-talk. From Bi-
ology To Concurrency and Back, 2010, 40–54. http://
doi.org/10.4204/EPTCS.19.3
3.Pathway linker, http://pathwaylinker.org/job.cgi?
j=1459047810.22901685706.
4.String network view, http://stringdb. org/newstring_cgi/
show_network_section.pl?
taskId=pkLCeLsyQJeT&allnodes=1
290 Abstract
Cells coordinate their biological function through secondary massager signals followed by several chemical, and electrical responses. These signals propagated on molecular
level may not the result of single receptor activity but several receptor signals may associated with one single downstream spiking signal. These receptors associated collective
interactions and the resulting response signal can be explained by prediction of cross –talk between such communicating receptor in direct or indirect manner. Here we report
crosstalk, direct/ indirect interaction of CDK5 with other secondary massager pathway by several computational and online database associated interaction tools. By the use of
String 10, Signalink 2.0, Pathway linker, KEGG pathway, EVEX database, Interologous interaction database, wiki pathway, ICR workspace, Ensamble and Expression atlas
we have demonstrated a number of protein-protein interactions and identified possible cross talk between their signals. From RCSB Protein databank initially two proteins
with PDB ID 1H4L and 4P91 for CDK5-P25 and Nogo1-R respectively were selected. By use of 3D molecular viewer/ Discovery studio 4.5. P-25 chains (C and D) were
removed. Ligands and water molecules associated with 1H4L were removed. Similarly with 4P91; water molecules and ligands were isolated. From online available tool
Cluspro (cluspro.bu.edu) by taking CDK5 as receptor and NogoR1 as its substrate; balanced, electrostatic favored, hydrophobic-favored, VdW+Elec interactions were
detected. From all these interactions 10 balanced interactions are depicted here. Interactions between amino acid of two proteins were identified in Gold suit
software.
Figure 1: Function of CDK5 in CNS Figure 2: Role of NgR1 in neuroprotection
Figure 3: CDK5R1 Crosstalk via pathway linker Figure 4: RTN4 Crosstalk via pathway linker
A B C
D E F
G
Figure 3: A. Interaction of CDK5 and NgR1; B. Protein overlapping before and after simulation; C. Interaction sites of CDK5 and NgR1; D,E,F,G. Dynamics of Interacted proteins from 0 to 10,000 fs in respect to PE, KE, TOT ENG and TEMP; H. Sequence homology after 10,000 fs simulation.
H
Table 1: Amino acids interactions
Figure 4. Possible interactions of NgR1 with CDK5.
Figure 5. Ramachandran plot of interacted CDK5-NogoR1 protein before (A) and after 10,000 fs (B) simulation.
A B A B C
Figure 6. Possible crosstalk of (A) GSK3β,(B) CDK5 and (C) NgR1/ Rtn4 by STRING network view