**Author details**

Silvana Giuliatti\*

Address all correspondence to: silvana@fmrp.usp

Faculty of Medicine of Ribeirão Preto - University of São Paulo, Brazil

## **References**

**Summary Tools**

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical

**modFold** https://www.reading.ac.uk/bioinf/ModFOLD/ **ProQ** http://www.sbc.su.se/~bjornw/ProQ/ProQ.html

**Q-sitefinder** http://www.modelling.leeds.ac.uk/qsitefinder/

**THREADER** http://bioinf.cs.ucl.ac.uk/software\_downloads/threader/

**PASS** http://www.ccl.net/cca/software/UNIX/pass/overview.shtml **SURFNET** http://www.ebi.ac.uk/thornton-srv/software/SURFNET/

**GOLD** http://www.ccdc.cam.ac.uk/products/life\_sciences/gold/

**RAPTOR** http://www.bioinformaticssolutions.com/raptor/downloadpricing/freetrial.html

The author would like to thank CAPES-PROEX and CNPq for financial support.

**GLIDE** http://www.schrodinger.com/products/14/5/

**MUSTER** http://zhanglab.ccmb.med.umich.edu/MUSTER/ **I-TASSER** http://zhanglab.ccmb.med.umich.edu/I-TASSER/

**metaPocket** http://projects.biotec.tu-dresden.de/metapocket/

**ROSETTA** http://www.rosettacommons.org/home

Applications

86

**SAVes** http://nihserver.mbi.ucla.edu/SAVES/

**AUTODOCK** http://autodock.scripps.edu/

**Derek/Meteor** https://www.lhasalimited.org/ **Raptorx** http://raptorx.uchicago.edu/

**Table 2.** Software tools and server web sites.

**Acknowledgements**

**Author details**

Silvana Giuliatti\*

**Phyre** http://www.sbg.bio.ic.ac.uk/~phyre/

Address all correspondence to: silvana@fmrp.usp

Faculty of Medicine of Ribeirão Preto - University of São Paulo, Brazil

	- [12] Huang, B., & Schroeder, M. (2006). LIGSITEcsc: Predictiong Ligand Binding Sites us‐ ing the Connolly Surface and Degree of Conservation. *BMC Structural Biology*, 6, Sep‐ tember, 19, 1472-6807.

[24] Laurie, A., & Jackson, R. (2005). Q-SiteFinder: an Energy-based Method for the Pre‐ diction of Protein-Ligand Binding Sites. *Bioinformatics*, 21(9), May, 1908-1916,

Computer-Based Methods of Inhibitor Prediction

http://dx.doi.org/10.5772/ 52334

89

[25] Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Dis‐ covery and Development Settings. *Advanced Drug Delivery Reviews*, 46(1-3), March,

[26] Lüthy, R., Bowie, J. U., & Eisemberg, D. (1992). Assessment of Protein Models with

[27] Mc Guffin, L. J. (2008). The ModFOLD Server for the Quality Assessment of Protein

[28] Milleer, R. T., Jones, D. T., & Thornton, J. M. (1996). Protein Fold Recognition by Se‐ quence Threading: Tools and Assessment Techniques. *The FASEB Journal*, 10(1), Janu‐

[29] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2004). AutoDock4 and AutoDockTools4: Automated Docking with Se‐ lective Receptor Flexibility. *Journal of Computational Chemistry*, 30(16), December,2009,

[30] Pontius, J., Richelle, J., & Wodak, S. J. (1996). Deviations from Standard Atomic Vol‐ umes as a Quality Measure of Protein Crystal Structures. *Journal of Molecular Biology*,

[31] Ramachandran, G. N., Ramakrishnan, C., & Sasisekharan, V. (1963). Stereochemistry of Polypeptide Chain Configurations. *Journal of Molecular Biology*, 7, July, 95-99,

[32] Rohl, C. A., Strauss, C. E., Misura, K. M. S., & Baker, D. (2004). Protein Sructure Pre‐

[33] Sali, A. E., & Blundell, T. L. (1993). Comparative Protein Modelling by Satisfaction of

[34] Söding, J., Biegert, A., & Lupas, A. N. (2005). The HHpred Interactive Server for Pro‐ tein Homology Detection and Structure Prediction. *Nucleic Acids Research*, 33(3), De‐

[35] Subramani, A., Wei, Y., & Floudas, C. A. (2012). ASTRO-FOLD 2.0: An Enhanced Framework for Protein Structure Prediction. *American Institute of Chemical Engineers*

[36] Sunitha, K., Hemshekhar, M., Gaonkar, S. L., Santhosh, M. S., Kumar, M. S., Basappa Priya, B. S., Kemparaju, K., Rangappa, K. S., Swamy, S. N., & Girish, K. S. (2011). Neutralization of Hanemorrhagic Activity of Viper Venoms by 1-(3-Dimethylamino‐

diction using Rosetta. *Methods Enzymol*, 383, 66-93, 0076-6879.

Spatial Restraints. *Journal of Molecular Biology*, 234, 779-815, 0022-2836.

Three-Dimensional Profiles. *Nature*, 356(6364), March, 83-85, 0028-0836.

Structural Models. *Bioinformatics*, 24, 586-587, 1460-2059.

1046-2059.

3-26, 0016-9409 X.

ary, 171-178, 1530-6860.

2785-2791, 0109-6987 X.

0022-2836.

264(1), November, 121-126, 0022-2836.

cember, W244-W248, 1362-4962.

*Journal*, 58(5), May, 1619-1637, 1547-5905.


[24] Laurie, A., & Jackson, R. (2005). Q-SiteFinder: an Energy-based Method for the Pre‐ diction of Protein-Ligand Binding Sites. *Bioinformatics*, 21(9), May, 1908-1916, 1046-2059.

[12] Huang, B., & Schroeder, M. (2006). LIGSITEcsc: Predictiong Ligand Binding Sites us‐ ing the Connolly Surface and Degree of Conservation. *BMC Structural Biology*, 6, Sep‐

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical

[13] Huang, B. (2009). MetaPocket: A Meta Approach to Improve Protein Ligand Binding Site Prediction. *OMICS: A Journal of Integrative Biology*, 13(4), August, 325-330,

[14] Jiang, X., Chena, L., Xua, J., & Yanga, Q. (2010). Molecular Mechanism Analysis of Gloydius Shedaoensis Venom Gloshedobin. *International Journal of Biological Macro‐*

[15] Jones, D. T., Taylor, W. R., & Thornton, J. M. (1992). A New approach to Protein Fold

[16] Jones, G., Willett, P., Glen, R. C., Leach, A. R., & Taylor, R. (1997). Development and Validation of a Genetic Algorithm for Flexible Docking. *Journal of Molecular Biology*,

[17] Kastenholz, M. A., Pastor, M., Cruciani, G., Haaksma, E. E. J., & Fox, T. (2000). GRID/ CPCA: A New Computational Tool to Design Selective Ligands. *Journal of Medical*

[18] Kelley, L. A., & Stemberg, J. E. (2009). Protein Structure Predicition on the Web: a Case Study using the Phyre Server. *Nature Protocols*, 4(3), February, 363-371,

[19] Klepeis, J. L., & Floudas, C. A. (2003). ASTRO-FOLD: A Combinatorial and Global Optimization Framework for Ab Initio prediction of Three-Dimensional Structures of Proteins from the Amino Acid Sequence. *Biophysical Journal*, 85(4), October,

[20] Krivov, G. G., Shapovalov, M. V., & Dunbrack, R. L. (2009). Improved Prediction of Protein Side-Chain Conformations with SCWRL4. *Proteins*, 77(4), December, 778-795,

[21] Larkin, M. A., Blackshields, G., Brown, N. P., Chenna, R., Mc Gettigan, P. A., Mc Wil‐ liam, H., Valentin, F., Wallace, I. M., Wilm, A., Lopez, R., Thompson, J. D., Gibson, T. J., & Higgins, D. G. (2007). Clustal W and Clustal X Version 2.0. *Bioinformatics*, 23(21),

[22] Laskowiski, R. (1995). SURFNET: a Program for Visualizing Molecular Surfaces, Cav‐ ities and Intermolecular Interactions. *Journal of Molecular Graphics*, 13(5), October,

[23] Laskowski, R. A., Macarthur, M. W., Moss, D. S., & Thornton, J. M. (1993). PRO‐ CHECK: a Program to Check the Stereochemical Quality of Protein Structures. *Jour‐*

*nal of Applied Crystallography*, 26(2), April, 283-291, 1600-5767.

tember, 19, 1472-6807.

*molecules*, 48(1), January, 129-133, 0141-8130.

267(6381), July, 727-748, 0022-2836.

Recognition. *Nature*, July, 358, 86-96, 0028-0836.

*Chemistry*, 43(16), August, 3033-3044, 1520-4804.

1557-8100.

Applications

88

1754-2189.

1097-0134.

2119-2146, 0006-3495.

323-330, 0263-7855.

November, 2947-2948, 1460-2059.


> propyl)-1-(4-Fluorophenyl)-3-Oxo-1, 3-Dihydroisobenzofuran-5-Carbonitrile. *Basic & Clinical Pharmacology & Toxicology*, 109(4), October, 292-299, 1742-7843.

**Chapter 4**

**New Perspectives in Drug Discovery Using Neuroactive**

Arthropods are one of the most ancient groups of animals in earth and their venoms have been responsible for their chemical defense in a very efficient way. Resulting from an in‐ tense and elaborated evolutionary process, venoms produced by arthropods have a very complex repertoire of biologically active molecules. When inoculated in mammals these molecules induce a wide range of systemic effects, including actions in the CNS. In mamma‐ lian CNS, venom compounds may either inhibit or stimulate with affinity and specificity structures such as: ion channels, neurotransmitter receptors and transporters [1-3]. Not sur‐ prisingly, these actions have attracted the attention of many investigators in search of tools to help the understanding of neural mechanisms as well as those in search of novel probes in CNS drug design for the last 20 years [3,4]. In addition to the growing interest in finding new neuroactive compounds, the improvement of proteomic and transcriptome techniques has stimulated great progress in the bioprospecting, enabling and accelerating the testing of new toxins in several animal models. Animal research aiming at the efficacy of peptides and acylpoliamines, isolated from arthropod venoms, have revealed the great potential of these compounds to treat various diseases, such as epilepsy, Parkinson's, Alzheimer's, chronic

According to World Health Organization (WHO), neurological and mental disorders are one of the greatest threats to public health not only for its direct and immediate effects, but also for the progressive nature of these diseases, often leading to disability and death [5]. The symptoms of most of these diseases are often well treated with a several pharmaceuti‐ cals, such as antidepressants, anxiolytics, anticonvulsants and analgesics. However, it is well known that neuroactive drugs may induce a complex range of adverse effects that limit the

> © 2013 Mortari and Siqueira Cunha; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 Mortari and Siqueira Cunha; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

**Molecules From the Venom of Arthropods**

Márcia Renata Mortari and

http://dx.doi.org/10.5772/ 52382

**1. Introduction**

pain and anxiety disorders

Alexandra Olimpio Siqueira Cunha

Additional information is available at the end of the chapter

