INPhINIT Incoming Fellowship – Drug Design targeting allosteric sites of proteins
jaime.rubio@ub.edu
RESEARCH PRODUCT / RESEARCH GROUP
Structure-based design and discovery of protein ligands have emerged as a new tool in medicinal chemistry. In particular, the knowledge of the three-dimensional structure of a protein can be used to derive new protein ligands with improved binding properties ( i.e. new drugs ). Within this approach, we need algorithms and methods to solve the following questions: What is the binding affinity of a novel ligand towards a receptor? What are the best conformations of a ligand to the binding site? What are the similarities of different ligands concerning their recognition capabilities? With which orientation will a ligand bind to the active site? We want to contribute to obtaining new answers for these questions and some problems concerning CANCER disease.
http://www.ub.edu/cadrugdesign/index.html
An important challenge in drug discovery concerns the determination of how a drug finds its target binding site. In particular, the identification of allosteric ligand-binding sites for selective inhibition of protein families with a high similarity has become an attractive approach for many biotech companies. A plethora of approaches has been developed to try to solve this problem being the different molecular dynamics versions those that have obtained the best results. However, the problem is far from being solved. Basically, because the potential energy surface (PES) of the ligand-protein system is a continuous function that depends on 3 times the number of atoms preventing an easy computational resolution of the problem. In this project, we will develop a novel method for conformational searching of relevant biological systems that relies upon the fact that it is possible to locate saddle points that surround a given minimum on a complex PES using the concerted atomic motions found in low-frequency vibrational modes.
The Modelling of Biological systems and Drug Design research group associated to the Materials Science and Physical Chemistry department at the University of Barcelona (UB) and to the Institute of Theoretical and Computational Chemistry (IQTCUB) was created in 2002. The group has now extensive experience in the field of Computational Chemistry and Molecular Modelling and in the use of structure-based drug design methodology for the design of new compounds with possible pharmacological activity. Taking advantage of our previous experience the group is also still working on the development of new computational tools to make easier the drug design process and to increase its effectiveness. The group promotes interdisciplinary research through collaborations with experimental groups working basically in targets related to cancer disease.
The group is seeking a PhD student with a degree in Chemistry, Physics or Biochemistry and with a Master related to the use of computational methods in Molecular Modeling. We are interested in bringing people with different motivations to develop cutting-edge Drug Design technologies to understand how a compound finds its binding site. The PhD student will develop new software using free resources, like openMM. The PhD student will perform a temporary stay in the zymvol company (www.zymvol.com) specialized in the design, development and application of molecular modeling software to enzyme discovery and optimization.
OTHER RELEVANT WEBSITES
Website of ZYMVOL company, specialized in the design, development and application of molecular modelling software to enzyme discovery and optimization