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Horacio Perez-Sanchez

Horacio Perez-Sanchez

Universidad Catolica San Antonio de Murcia (UCAM), Spain

Title: Virtual screening for the discovery of novel bioactive compounds: Application to blood anticoagulants and nutraceuticals

Biography

Horacio Pérez-Sánchez graduated in Theoretical and Computational Chemistry from the University of Murcia (Spain) in 1999, where he also obtained his PhD degree in 2006, which consisted in the development and implementation of computational methodologies for the study of macromolecular systems. He performed research in several European Institutions such as the Institute of Structural Biology (CEA, Grenoble, France), and at the Karlsruhe Institute of Technology (Karlsruhe, Germany). Currently he is full-time Researcher and Principal Investigator of the "Bioinformatics and High Performance Computing" research group at the Catholic University of Murcia (Spain). He has co-authored more than 50 international conference contributions and journal papers, book chapters and European patents. He has served as a reviewer for several conferences/journals/book editorials. His primary research interests are in the areas of bioinformatics, mainly drug discovery, and its exploitation in parallel architectures. He has participated in several projects funded by the European Commission and the Spanish and German Ministries of Science.

Abstract

The discovery of novel anticoagulants without side effects is one of the main problems of haemostasis. Ever since the discovery of the anticoagulant properties of hirudin from the leech saliva, the increasing relevance of thromboembolic diseases has encouraged a continuous search for new compounds with anticoagulant activity, which have led to the development of the new commercially available anticoagulants. One of the targets for prophylaxis and treatment of thromboembolic diseases is the plasma anticoagulant antithrombin. This protein circulates in blood in a metastable conformation, in which the reactive centre loop is partially inserted and is only activated by heparin and heparan sulfate glycosaminoglycans on the injured subendothelium. Accordingly sulfated polysaccharide heparin chains with different size, from unfractionated to the essential pentasaccharide, have been used with more or less success in anticoagulant therapy and thromboprophilaxis. In the last decades new molecules able to bind antithrombin have been identified. The strategies used in this search have been based mainly on the synthesis or chemical modification of existing drugs, or in the application of natural compounds with similar properties to those currently used. Examples for such compounds are lignins and flavonoids, highly sulfated small organic ligands that seem to have similar properties to heparins. Therefore, the discovery of novel or improved drugs for given diseases or special groups of patients, is a very slow and expensive process. Nevertheless, recent results obtained by the speaker demonstrate the discovery using Virtual Screening (VS) of a novel molecular scaffold, different to the previous ones based on heparin. Using this alternate approach, a large database of millions of chemical compounds is screened in-silico and affinity-ranking is used to identify some at least weakly-binding molecules for further refinement. Aided by ever-increasing computational power, VS is an appealing and cost-effective approach to tap into the wealth of available structural information. Consequently, novel and enhanced VS methodologies, conveniently exploited in innovative drug discovery strategies can lead to significant and quantifiable developments. In addition, examples of the application of this methodology to the characterization and discovery of bioactive compounds present in food will be given.