Spider Venoms by P. Gopalakrishnakone Gerardo A. Corzo Maria Elena de Lima & Elia Diego-García

Author:P. Gopalakrishnakone, Gerardo A. Corzo, Maria Elena de Lima & Elia Diego-García
Language: eng
Format: epub
Publisher: Springer Netherlands, Dordrecht

Docking and Molecular Dynamics Applied to the Study of Spider Toxins

The observation of a 3D structure of a peptide, a protein, a biological membrane or any other biochemical system depends on a series of complex steps that are sometimes impossible to achieve. Aside from the experimental difficulties, the importance of the in silico techniques of visualization, representation, and simulation of biochemical systems has grown because they can either aid in the explanation of experimental results or can be used to explain and predict the structural and energetic behavior of biochemical systems without any experimental testing.

Molecular docking involves an initial study of the interaction between two systems, which can be two proteins, a ligand of a non-protein structure and its receptor, chains of DNA, RNA, etc. The affinity of the interaction is evaluated by functions that result in an estimation of the interaction energy. Therefore, when a molecular docking procedure is carried out it is given as a response the possible structure of an interaction between the ligand and receptor. For detailed reviews of the procedures in molecular docking see, for example, the articles by Guedes et al. (2013) and Ewing and Kuntz (1997).

The results obtained by the docking present a series of “positions” that express the higher probabilities of interaction between the ligand and the receptor. However, even using a flexible docking technique (where the receptor and ligand are allowed to move), a complete simulation of the interaction forces that exist in a molecular system cannot be performed. Hence, molecular dynamics (MD) simulations normally follow the initial results obtained with docking.

As the name implies, MD simulations are used to describe the behavior of a molecular system evolving under the action of the forces because of the intra- and intermolecular interactions. Basically, the MD utilizes Newton’s laws of motion and the methods of statistical thermodynamics to obtain thermodynamic and structural data and with the continuous improvement of hardware and software, larger systems are being simulated for longer periods of time. For an interested reader, noteworthy reviews of the techniques of MD have been published, including the works of Karplus and McCammon (2002) and Hansson et al. (2002).

With the purpose of reviewing the possible interactions of spider toxins with biological systems, Corzo and Escoubas (2003) described the biological effect of pharmacologically active peptides obtained from spider toxins. Among the effects described are the interactions with the voltage-gated sodium, potassium, and calcium channels in addition to the glutamate receptor channel, interaction with lipidic layers, etc. Later, Bosmans and Swartz (2010) described the biological effects of spider toxins acting on sodium channels, reporting results regarding the action of the toxins in one or more channels and the possibility of using these toxins as a suitable way to obtain new drugs.

To understand all of the different interactions between the toxin and receptor, it is necessary to examine the 3D structure of the systems. However, despite knowledge of these 3D structures being fundamental, the process by which they can be obtained is often very hard difficult and indirect techniques for obtaining such structures are useful.

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