Supercomputers and distributed computing help Russian scientists to create new pharmaceuticals, which fight thromboses, very quickly. Researchers found substances, which may become the basis for new effective therapy against thromboses and components for blood substitutes.

Blood clots or thrombs often form in vessels of people with vascular diseases or after hemodialysis and blood transfusion. Key enzyme in the complex system of blood coagulability is called thrombin. Today most common agent, preventing clot formation, is heparin; however, heparin only helps natural thrombin inhibitor – antithrombin. When patient’s blood has little antithrombin, heparin is ineffective, and sometimes even dangerous (when a patient has specific blood disorders). The solution exists – patients require injections of direct thrombin inhibitor. Modern medicine knows only one synthetic direct thrombin inhibitor, allowed for clinical use – argatroban. That is why development of other pharmaceuticals with mentioned properties is a pressing task.

Russian scientists faced the challenge by means of molecular modeling. Pharmaceuticals target proteins, which are connected with some pathological process, leading to a disease. Molecule of an inhibiting substance binds with active centre of target protein and blocks it. This inhibiting molecule was what researchers were looking for.

Researchers performed search for effective thrombin inhibitors by means of the software system KeenBASE and original software SOL, both developed in the Science and Research Computer Centre of Moscow State University. Said software “placed” candidate molecules inside the active centre of thrombin and calculated their bonding energy with the protein. The higher bonding energy was, the stronger barrier tested molecule appeared to set for thrombin activity, thus the more effective future therapy would be. Scientists used the method of distributed computing and several supercomputers, located in various Russian cities for their calculations. Only 18 months were required for calculating several thousands of candidate molecules, testing most promising substances and forwarding new pharmaceuticals for further testing on laboratory animals.

As the result of such a huge amount of calculations Russian scientists synthesized and patented new class of synthetic low-molecular thrombin inhibitors, which are much more effective than argatroban. Moreover, these substances are suitable for making new blood substitutes. Thank to supercomputers the enormous work was done in very short time, and its expenses were significantly less than in case of “ordinary” method of searching for biologically active substance. During the experiment scientists performed calculations for about 6 thousand molecules, and first promising candidate appeared under number “20”. “Ordinary” techniques, which are common for various pharmacy enterprises, require synthesizing and testing of all 6 thousand molecules.

Source: Science & Life

Kizilova Anna