answers to queries:

1) Modeller is a good software..and since you are good in using it you can begin with it...I'll suggest you should try also online homology modelling servers at leading stuctural bioinfomatics institute sites....The ease levels of 'in silico' analysis will depend upon how much is the simlarity among the nine 'so called MSP protein' you are studying...If there is High similarity among some of them making strutures based on homology modelling modelling will be easy and then you can overlap the generated strutures with the experimentally determined one to focus of the structural differences in the regions of interest...If some of them are highly disimilar...try going step by step..identify the conserved secondary structure elements first ..model the structure around those regions and do enerygy minimizations in other not so constrained regions...But finally some 'wet lab' validations are always the best way to prove what you predict

2) Phylogentic relations ships among the organisms containing a particlualar MSP proteins should be simple...use your sequence..in BLAST at NCBI/FASTA at EBI to find out organisms conatining that gene..select the number of organisms for which you want to infer the relationships... and you should be able to do this online or offline...both are feasible..

3) If complete genomes of the species of your interest are available...try doing comparative analysis of genes and pathways at TIGR website..

Can elaborate your last query 'metagenomics and sequencing all genes'''...with nested primers''...it has too many missing links..

You are lucky to have one of structure of protein of your interest...the project will definitely involve intensive 'wet lab' and 'in silico' approaches...but you can initiate by using 'homology modelling' of other MSP proteins...

Thank you,, as in case of modelling I m gud at modeller software ,,but could u plz suggest me some other softwares for modelling ,,,nd how can i predict phylogentic relationship among species with msp protein online ,,,u r free to suggest some other approches too.. Thanks again :)

or can i have Metagenomics ANALYSIS .??

in case of wetlab yep ,i have to do sequencing of all genes with Nested pcr anaysis etc

answers to queries:

1) Modeller is a good software..and since you are good in using it you can begin with it...I'll suggest you should try also online homology modelling servers at leading stuctural bioinfomatics institute sites....The ease levels of 'in silico' analysis will depend upon how much is the simlarity among the nine 'so called MSP protein' you are studying...If there is High similarity among some of them making strutures based on homology modelling modelling will be easy and then you can overlap the generated strutures with the experimentally determined one to focus of the structural differences in the regions of interest...If some of them are highly disimilar...try going step by step..identify the conserved secondary structure elements first ..model the structure around those regions and do enerygy minimizations in other not so constrained regions...But finally some 'wet lab' validations are always the best way to prove what you predict

2) Phylogentic relations ships among the organisms containing a particlualar MSP proteins should be simple...use your sequence..in BLAST at NCBI/FASTA at EBI to find out organisms conatining that gene..select the number of organisms for which you want to infer the relationships... and you should be able to do this online or offline...both are feasible..

3) If complete genomes of the species of your interest are available...try doing comparative analysis of genes and pathways at TIGR website..

Can elaborate your last query 'metagenomics and sequencing all genes'''...with nested primers''...it has too many missing links..

Prefer crystal and solution structure for drug development by that protein ligand intraction

@Ajay sir : i mean to say i will be doing sequencing Pcr of all 9 gens... Thanks for info lookin forward with your given ideas ,..also i am planning to do at Gene level too !! like genome annotation, snp variant analysis. ..would you suggest

some approches at gene stage ???,, where i could do genome analysis.

@priyanka ..

Hi I Just tried to give some ideas based on your queries...there are definietly many other ways to approach to the answers to your queries..for both proteomic and genomic analysis..but one has to take one step at a time..weigh thoroughly the available approaches and take the right step forward...I can definitely give some inputs about analysis at gene/genome level...but I'll request you to keep your queries specific and focus one point at a time....please don't mind ..but in my opinion 'genome annotation', 'snp variant analysis' and 'genome analysis' are very big and intensive objectives and one cannot find solution at a single site..a variety of anaylsis using different types of tools will be required....

Specific drug development without crystallography !!!!

You can check this article to see whether your proteins of interest are belonging the the list of valid drug target and use the TDR database.

"Identification of Attractive Drug Targets in Neglected-Disease Pathogens Using an In Silico Approach"

Very broadly, for target identification, select proteins in the parasite, which are not present in human, study their role in the parasite, pathways involved Find out active sites. Design a ligand, best suited for the active site/s or search databases for synthetic/natural molecules as suggested by YOANN.

Please see this publication in a OPEN ACCESS Journal.if you can not access full paper, Please do let me know. Every thing is given step by stem.

Prediction of Medicinal Properties of Marine Biota using Computational Bioinformatics Techniques

Authors: S. Gupta and R.K. Sharma

Asian Journal of Biological Sciences 4 (8): 575-590, 2011. 2011; 4(8):575-590. (published)

For Malaria also I did some in-silico studies and found out some very interesting plants not reported for antimalarial properties.

Additionally, In my opinion pl search Chemical abstract and other databases and make your own specialized databases on for 1. Find out targets/proteins in malarial parasite. 2 Then search small drug-able chemical entities reported for antimalarial /antiparasitic properties.3. Search for proteins interacting with the target -protein-protein interaction, 4. Search on Systems biology and malarial parasite 5. Search on Molecular modelling and malarial parasite. ,,,,,,,,

Use Endnote or Reference manager to manage your database/s

This all will help you to know the state of the art and then picking up targets/ligands, and writing a paper.

@Sereno

Hi..there is still not a specific protocol for making protein crystals for Crystallography...making protein crystals is still an ART...there is nothing wrong in 'taking a step forward' based on all the available infromation and 'wet lab' or 'in silico' resources...Thats what we do most of the times..even in planning our experiments...

dear priyanka..

at systems biology level, either you can do the metabolic reconstruction, or signaling reconstruction or simply develop the protein interaction network and do a random graph analysis or Power graph analysis to find the hub of the interactome..

If it is the metabolic reconstruction, you have to find a rate limiting step and target that protein.

as for as I understand your problem, you want to identify the choke point enzymes or regulatory pathways.

for this I would suggest you to do a metabolic reconstruction and analysis.

But this needs extensive curation and analysis and is time consuming. but still a very valuable data that you can produce.

but if you already made up your mind to go ahead with the msps then no need to think systems biology.

just do a sequence analysis for five orthologs for all the 9 sequences, see the level of conservartion.

pocket geometry, and then visit TTD database to get a probable drug to your target of interest. then if you want you can use MArvin sketch for generating the conformers, use them for virtual screening.

is there any lab who do antimalarial activity for comparative in wet and Dry labs

Shivakrishna pabba dr. Rajeshwara achur, associate professor at department of biochemistry, kuvempu university is cuurently working on this aspect

Thank you santosh kumar but will he help me out if i send him sample ,can you send me his email id

@Ajay sir : i Agree wat you say ,,instead of focusing at multilevel ,i should carry on in one way.

@Ravi sir : Than you .. i read your research paper ,,nd yeah its freely accessible at http://docsdrive.com/pdfs/knowledgia/ajbs/2011/575-590.pdf

it will definatly help me for further steps .. on which platform you have identified ligands again pyruvate kinase and trypanothione reductase .. I mean all your steps were perform on Windows or Linus/unix or any other ??/

@Ajay Saini To my personnal experience making specific ligand without crystal structure have generated a large amount of in vitro validation of these ligands for, in fine when we get crystal, just realize that our enzyme have a special conformation in the catalytic site that explain why our lignad doesn't work!!!! Therefore generating ligands without good crystallographic data is tricky.

@Sereno Denis

HI Sereno....I completely agree with you on this aspect....but my only point was ..if someone does not have a crystallographic data for a protein/enzyme.....he/she should not sit and wait ....but should try whatever else also they can do using whatever tools/information/resources are possibe...for the MSP protein it was mentioned above that one structure is available and it may serve as a good template for the other similar proteins...you never know

in 2010 December, we compiled a comprehensive database on bioinformatics and malarial/filarial/leishmanial parasites. Any one interested can contact me

@Ravi Sharma

Dear Sir this will be a very useful information for this forum on Malaria

@ Priyanka Patel

All the work mentioned in the above paper was done on windows platform using all the tools available Free on the Net. Except some work on homo-logy searches and Bibliographic database searches were done on SciFinder.

@Ravi Sharma, I am personnaly interrested on such database. On an other part I am also greatly interrested on chemist that have some idea on how to develop good ligand for Nicotinamidase of Trypanosomatidae. Until now all our approach have failed!!!!!!

@ Patel..If you have 1-9 MSP sequence then go 4 homology modeling using Modeller on personal computer or server available freely. After doing modeling refine yor structure by Ramachandran plot or Pro Q/ ERRAT quality factor, after that go for active site prediction using CASTP or any other then start docking with your drug by Molegro Virtual Docker or Argus lab or any other which is authentic software.

Gud luck...

Can any one suggest me a good invitro antimalarial assay procedure

The SYBR Green assay works well.

Antimicrob Agents Chemother. 2007 Jun;51(6):1926-33. Epub 2007 Mar 19.

Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening.

Johnson JD, Dennull RA, Gerena L, Lopez-Sanchez M, Roncal NE, Waters NC.

hey priyanka there are lots of databses available to check in the pathway and where to work upon...log onto KEGG and u will get a fair ides of all...then check in sites like MEDminer, swissprot etc to come out with what appproach u really want to work upon and at what stage of the pathway

@Ravi Sharma i am also interested in accessing the database on Malaria